Kufuna Kugwiritsa Ntchito Mankhwala: Kuyanjanitsa Khalidwe ndi Kukhalanso Kufuna Kugwiritsa Ntchito Mankhwala Osokoneza Bongo (2011)

Yofalitsidwa pa intaneti isanasindikizidwe pa Epulo 13, 2011, doi: 10.1124/pr.109.001933 Kuwunika kwa Mankhwala vol. 63 no. 2 348-365

Jeffery D. Steketee ndi

Peter W. Kalivas

Dipatimenti ya Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee (JDS); ndi Dipatimenti ya Neuroscience, University University ya South Carolina, Charleston, South Carolina (PWK)

David R. Sibley , MKONZI WOPHUNZIRA

+ Mabungwe a Olemba

  1. Maadiresi a:
    Jeff Steketee, Dipatimenti ya Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163. Imelo: [imelo ndiotetezedwa]
- Yendetsani Nkhaniyi

Kudalirika

Kuwonetsedwa mobwerezabwereza ndi mankhwala osokoneza bongo kumapangitsa kuti magalimoto apitirize kuyankhidwa ndi mankhwalawa, chodabwitsa chimatchedwa khalidweal sensitization. Nyama zomwe zimazimitsa kuphunzitsidwa kuti azidzilamulira okha zimangobwereranso ku mankhwala osokoneza bongo, kupanikizika, kapena kuponderezedwa. Kuphatikizidwa pakulimbikitsa anthu kuti ayambe kutsata mankhwala osokoneza bongo kumatsutsana. Kuwongolera uku kumapangitsa kuti anthu azikhala ndi mankhwala osokoneza bongo komanso obwezeretsedwa monga zochitika zokhudzana ndi khalidwe lawo, ndipo oyendetsa magetsi a neuralchemistry, neurochemistry, ndi neuropharmacology yomwe ikuyang'aniridwa ndi zitsanzo ziwiri zidzalongosoleredwa, poyerekeza, ndi zosiyana. Zikuwoneka kuti ngakhale kulimbikitsidwa ndi kubwezeretsedwa kumaphatikizapo kudumphadumpha ndi machitidwe a ubongo ndi njira zothandizira anthu, udindo wa kubwezeretsedwa umakhalabe wosadziwika. Komabe, akutsindika kuti kulimbikitsabe kumakhalabe chitsanzo chothandizira kudziwa kuti njira zowonongeka ndi zowonongeka, ndipo zitsanzo zimaperekedwa kuti deta kuchokera kufukufuku wothandizira amachititsa kuti pakhale mankhwala osokoneza bongo omwe adayesedwa pa zinyama zobwereranso ndi anthu omwe amamwa mankhwalawa.

I. Ndondomeko

Kugwiritsa ntchito mankhwala osokoneza bongo ndi vuto losatha komanso lokhalitsa. Kafukufuku wochuluka wokhudza njira zomwe zimayambitsa vuto la chizolowezi cha ubongo wakhala ukupitilira kwa zaka 3 zapitazi. Ngakhale kuti pali khama limeneli, pali njira zochepa zochiritsira zomwe zingathandize pochiza kudalira mankhwala osokoneza bongo. Mitundu ya mankhwala osokoneza bongo yomwe imapezeka m'zinyama imaphatikizapo kupereka mankhwala osadziletsa (omwe amaperekedwa ndi anthu ena) komanso osadziletsa (omwe amaperekedwa ndi anthu ena). Mpaka kumapeto kwa zaka za m'ma 1990, maphunziro okhudza kusokonekera kwa mitsempha chifukwa cha mankhwala osokoneza bongo ankayang'ana kwambiri pakuwunika zotsatira za mankhwala osokoneza bongo mobwerezabwereza (monga, kukhudzidwa) pa dopamine ndi glutamate systems ( Kalivas ndi Stewart, 1991 ; Vanderschuren ndi Kalivas, 2000 ). Ngakhale kuti kupereka mankhwala osadziletsa kwapereka zambiri zokhudza momwe mobwerezabwereza mankhwala osokoneza bongo amasinthira ntchito ya mitsempha, sizimavomerezedwa nthawi zonse kuti deta iyi imaneneratu kusokonekera kwa mitsempha komwe kumakhudzana ndi kupereka mankhwala osokoneza bongo. Chifukwa chake, kafukufuku waposachedwapa wayang'ana kwambiri pa kudziletsa mankhwala osokoneza bongo komanso, makamaka, kubwezeretsa khalidwe lofunafuna mankhwala osokoneza bongo. Kusankha chitsanzo ichi kumachokera pa lingaliro lakuti mankhwala ochizira chizolowezi adzalowererapo kuti apewe kubwereranso, komwe khalidwe lobwezeretsa limatanthauza chitsanzo ( Epstein et al., 2006 ). Mitundu yonse yowunikira ndi kubwezeretsanso imayesa momwe mobwerezabwereza mankhwala amakhudzira ntchito ya mitsempha, kusiyana kwakukulu ndi momwe mankhwalawa amaperekedwera. Chifukwa chake, ndemanga iyi idzayerekeza ndikusiyanitsa zotsatira za mitsempha ya mankhwala m'njira zokhazikika komanso zosakhazikika za chizolowezi zomwe zimagwiritsidwa ntchito pophunzira zotsatira za mitsempha za chizolowezi. Kenako timafufuza mafunso okhudzana ndi kusinthana ndi kutsimikizika kwa chitsanzo chilichonse ndi cholinga chodziwa kuchuluka kwa kutsimikizika komwe kutsimikizika kwa khalidwe komwe kumachitika chifukwa chobwerezabwereza mankhwala osakhazikika kumapereka kufalikira kwa mitsempha komwe kumayambitsa kubwezeretsedwa kwa kudzilamulira kwa mankhwala osakhazikika. Kuphatikiza apo, ngati kukhudzidwa kwa khalidwe ndi gawo lobwezeretsa khalidwe lofunafuna mankhwala kudzaganiziridwanso.

II. Malingaliro

A. Kusokoneza

Yankho lothandizira kuchitsimikizidwe, pambuyo pobwerezedwa mobwerezabwereza, limatchedwa kukulimbikitsidwa (Robinson ndi Becker, 1986; Kalivas ndi Stewart, 1991). Ponena za mankhwala osokoneza bongo, kudzikweza kwa khalidwe kumatanthauzidwa ndi kuwonjezereka kwa magetsi komwe kumachitika mobwereza mobwerezabwereza, kuwonetsera kwa mankhwala enaake. Kulimbikitsanso khalidwe ndi chinthu chokhalitsa; malingaliro owonjezereka amakhalidwe aperekedwa kuti apitirire kwa chaka chimodzi (Paulson et al., 1991). Zinthu zingapo, kuphatikizapo chiwerengero cha mankhwala, kusiyana pakati pa mankhwala, mlingo, kugonana, zaka, ndi chibadwa, zingakhudze mphamvu ya kuyalimbikitsa khalidwe (Zolemba ndi Contel, 1983). Kulimbikitsidwa kwa khalidwe kumachitika chifukwa cha cocaine, amphetamine, morphine, ethanol, nikotini, ndi D9-tetrahydrocannabinol (Joyce ndi Iversen, 1979; Robinson ndi Becker, 1986; Benwell ndi Balfour, 1992; Cunningham ndi Noble, 1992; Post ndi al., 1992; Cadoni et al., 2001). Kuwonjezera apo, kuwonetsetsa pakati pa mankhwalawa kwawonetsedwa. Mwachitsanzo, zinyama mobwerezabwereza zimawonekera kwa Δ9-tetrahydrocannabinol inachititsa kuti anthu azikhala ndi khalidwe lolimbikitsa la morphine (Cadoni et al., 2001), pamene zinyama zambiri zomwe zinkatchulidwa ku ethanol zinalimbikitsidwa ku cocaine ndi mosiyana (Itzhak ndi Martin, 1999), ndi zinyama mobwerezabwereza zowonekera kwa amphetamine zinalimbikitsidwa ku morphine (Lett, 1989; Vezina et al., 1989; Vezina ndi Stewart, 1990). Kuwonjezera apo, nyama zomwe zili ndi mbiri yobwerezabwereza ku toluene, kudzera mu kutsekemera, zinawonetsa kuchitidwa molimbikitsa kwa cocaine (Beyer et al., 2001). Izi zikusonyeza kuti njira zomwe zimagwirizanitsa zimapangitsa kuti anthu azikhala olimbikitsa khalidwe, ngakhale kuti magulu osiyanasiyana a mankhwala ali ndi malo osiyana siyana mu ubongo.

Kukula kwa kukhudzidwa kwa khalidwe kungapatulidwe m'magawo awiri: kuyambitsa ndi kufotokozera. Kuyambika ndi zochitika za mitsempha zomwe zimayambitsa kukhudzidwa kwa khalidwe, ndipo kufotokozera ndi zotsatira za nthawi yayitali za zochitika zoyambirira izi ( Kalivas ndi Stewart, 1991 ). Kuyambika nthawi zambiri kumalumikizidwa ndi dera la ventral tegmental (VTA 1 ), ndipo kufotokozera kumagwirizanitsidwa ndi nucleus accumbens. Chilengedwe chingakhudze kuyambika ndi kufotokozera kwa kukhudzidwa kwa khalidwe. Chifukwa chake, nyama zomwe zimakumana ndi mankhwala osokoneza bongo monga cocaine, amphetamine, kapena morphine mobwerezabwereza panthawi yoyambitsa zimasonyeza kukhudzidwa kwamphamvu kwambiri zikakumananso ndi mankhwala osokoneza bongo m'malo omwewo (ophatikizidwa) monga momwe zidakhalira ndi mankhwala osokoneza bongo panthawi yoyambitsa, poyerekeza ndi nyama zomwe zidayesedwa m'malo omwe anali osiyana (osaphatikizidwa) ndi omwe adagwiritsidwa ntchito panthawi yoyambitsa ( Vezina et al., 1989 ; Anagnostaras ndi Robinson, 1996 ; Wang ndi Hsiao, 2003 ; Mattson et al., 2008 ; Vezina ndi Leyton, 2009 ). Kuzindikira khalidwe m'malo ogwirizana nthawi zambiri kumatchedwa kuzindikira kumadalira chikhalidwe m'malo modziwitsa kudalira chikhalidwe, komwe kumachitika mu njira yosalumikizana. Kuzindikira kudalira chikhalidwe kwanenedwanso kuti kumachitika ( Vezina et al., 1989 ).

Kuwongolera khalidwe kumayesedwa kawirikawiri poyang'anira ntchito yogwira ntchito. Mukamayang'anitsa kuyendetsa galimoto, mobwerezabwereza kuwonetsa mankhwala kumabweretsa kuyankha kochititsa chidwi kwambiri kwa magalimoto. Kuzindikiritsa kwa amphetamine ngati psychostimulants kungapitirize kuwonetsa ngati khalidwe lolimba lomwe limapikisana ndi kutha. Mwachitsanzo, pamene makoswe amalimbikitsidwa kwambiri ndi amphetamine (mwachitsanzo, 2.0 mg / kg ip), amasonyeza kuchepetsa koyamba pa ntchitoyo poyankha mpikisano wa amphetamine, potsatira chiwerengero cha kuchepetsa kuchepa kwa ntchito (Leith ndi Kuczenski, 1982). Kulimbikitsanso khalidwe kumayesetsanso kupyolera mu malo okonda malo (CPP) kapena kugwiritsira ntchito mankhwala osokoneza bongo. Mu CPP paradigm, kulimbikitsidwa kumawonetseredwa ngati nthawi yowonjezera yogwiritsidwa ntchito mankhwala osokoneza bongo. Motero cocaine, amphetamine, ndi morphine-yomwe inachititsa kuti CPP ikhale yowonjezereka m'zinyama zomwe zili ndi mbiri yobwereza mobwerezabwereza ku mankhwalawa (Lett, 1989; Shippenberg et al., 1996). Kuphatikizidwa kotheka kuzipangidwe ka mankhwala osokoneza bongo nthawi zambiri kumatsimikiziridwa ndi kuthekera kwa kubwereza mankhwala osokoneza bongo mobwerezabwereza pofuna kupititsa patsogolo kugwiritsira ntchito mankhwala osokoneza bongo, kugwiritsa ntchito mankhwala osokoneza bongo, kapena kugwiritsira ntchito mankhwala osokoneza bongo pofuna kuchepetsa mphamvu zothandizira ogulitsa mankhwala osokoneza bongo jekeseni wa mankhwala (Vezina, 2004). Poyamba poonetsa kuti nyama zomwe zili ndi mbiri ya experimenter-yomwe imayambitsa amphetamine, yomwe inachititsa kuti anthu azikhala ndi mphamvu zothandizira, amasonyeza kuti amphetamine amadzipangira okha (Piazza et al., 1990). Kuwonjezera pamenepo, chisanafike kwa amphetamine, 3,4-methylenedioxy methamphetamine, kapena nicotine yowonjezera chiwopsezo cha kudziletsa kwa cocaine (Horger et al., 1992; Fletcher et al., 2001). Kafukufuku wotsatira anawonetsa kuti zinyama zomwe zili ndi mbiri ya intravenous cocaine kapena heroin zokhazokha zikuwonetseratu kuyankhidwa kwa magalimoto poyambitsa njira yothetsera vuto la mankhwala omwe amadzipangira okha (Hooks et al., 1994; Phillips ndi Di Ciano, 1996; De Vries et al., 1998b; Zapata et al., 2003). Kuonjezera apo, adasonyezedwa kuti pamene magalimoto oyendetsa galimoto akuyang'aniridwa panthawi yomwe akudzilamulira okha, kulimbikitsidwa ndi zolimbikitsa za heroin (Marinelli et al., 1998). Nyama zomwe heroin inadziperekanso zimasonyezeratu kuti zimapangitsa kuti anthu asamangokhalira kupuma (amphetamine)De Vries et al., 1998b). Pomalizira pake, tawonedwa kuti kachitidwe kowonjezereka, kosasinthika kwa amphetamine kumapangitsa kuti zipangizo zowonjezera za amphetamine ndi cocaine zikhale zolimba,Mendrek et al., 1998; Suto et al., 2002; Vezina et al., 2002). Kuwonjezera apo, kafukufuku wasonyeza kuti kuyandikira binge cocaine kudziyendetsa bwino ndikutsatidwa ndi kudziletsa kumathandizanso kuti cocaine isamangidwe (Morgan ndi Roberts, 2004; Morgan et al., 2006).

B. Kubwerera / Kubwezeretsanso

Maphunziro a zamankhwala omwe afotokozedwa pamwambapa akugwirizana ndi kuperekedwa kwa mankhwala mobwerezabwereza kosalekeza komwe kumabweretsa chidwi cha kusonkhezeredwa ndi mankhwala, kukonda malo, komanso kulimbitsa mankhwala. Komabe, mbali yovuta kwambiri ya chithandizo cha kuledzera mwina ndikupewa kubwereranso ( O'Brien, 1997 ). Kubwereranso kwachitika m'maphunziro a nyama kudzera mu njira zobwezeretsera kufunafuna mankhwala mwa nyama zomwe zasiya maphunziro odzipangira mankhwala (kuti muwonenso, onani Epstein et al., 2006 ). Maphunziro awa nthawi zambiri amaphatikizapo kukhazikitsa yankho la wochita opaleshoni (monga, lever press kapena nose poke) la mankhwala, kutha kwa operand iyi, kenako ndikubwezeretsa khalidwe la wochita opaleshoni. Mitundu itatu imagwiritsidwa ntchito kwambiri m'maphunziro obwezeretsa. Izi zikuphatikizapo 1) chitsanzo cha pakati pa gawo, momwe kudzipangira, kutha, ndi kubwezeretsanso kumachitika masiku osiyanasiyana; 2) chitsanzo cha mkati mwa gawo, momwe kudzipangira, kutha, ndi kubwezeretsanso kumachitika tsiku lomwelo; ndi 3) chitsanzo cha pakati, momwe kudzipangira kumachitika tsiku losiyana ndi kutha ndi kubwezeretsanso ( Shalev et al., 2002 ). Pogwiritsa ntchito mitundu iyi, zawonetsedwa kuti pambuyo poti kukanikiza kwa lever komwe kunalimbikitsidwa kale ndi cocaine kwatha, khalidweli likhoza kubwezeretsedwanso ndi jakisoni wa cocaine priming ( de Wit ndi Stewart, 1981 ). Zomwe zapezekanso zanenedwa za heroin, nicotine, ndi amphetamine ( de Wit ndi Stewart, 1983 ; Chiamulera et al., 1996 ; Ranaldi et al., 1999 ). Kuphatikiza apo, monga kukhudzidwa kwa cross-sensitivity, komwe kwafotokozedwa mu gawo II.A, kubwezeretsedwa kwa kukanikiza kwa lever komwe kunathandizidwa ndi cocaine kale kungayambitsidwe ndi amphetamine ndi morphine ( de Wit ndi Stewart, 1981 ). Komabe, kukanikiza kwa heroin ndi ethanol kunalephera kubwezeretsa kudzilamulira kwa cocaine ( de Wit ndi Stewart, 1981 ). Kuwonjezera pa kubwezeretsedwanso kwa mankhwala osokoneza bongo, kubwereranso ku chilengedwe chokhudzana ndi kudzipatsa mankhwala mwa nyama zomwe sizikutha (nkhani), zizindikiro zomwe kale zinkagwirizanitsidwa ndi kulowetsedwa kwa mankhwala, kapena kupsinjika maganizo kwambiri kungabwezeretse khalidwe lofunafuna mankhwala osokoneza bongo ( de Wit ndi Stewart, 1981 ; Shaham ndi Stewart, 1995 ; Meil ​​ndi See, 1996 ; Crombag et al., 2002 ). Kubwezeretsedwanso kwa mankhwala kungakhudzidwe ndi zinthu zingapo, kuphatikizapo maphunziro a chakudya musanaphunzire mankhwala osokoneza bongo, kugwiritsa ntchito mankhwala osakhazikika panthawi yophunzira, kuchuluka kwa mankhwala omwe amatengedwa panthawi yophunzira, ndi nthawi yoti munthu asiye kumwa mankhwala asanayesedwe kubwezeretsedwa ( Shalev et al., 2002 ).

Kuwonjezera pa njira yodzilamulira yokha ya mankhwala, njira ya CPP yagwiritsidwanso ntchito pophunzira kubwezeretsedwa kwa mankhwala. Mu njira ya CPP, nyama zimakumana mobwerezabwereza ndi malo amodzi osiyana ndi mankhwala osokoneza bongo ndi malo ena osakhala ndi magalimoto. Zikapatsidwa mwayi wolowa m'zipinda zonse ziwiri, nyama nthawi zambiri zimakonda malo omwe kale anali ndi mankhwala osokoneza bongo. Kafukufuku wakale wasonyeza kuti zikatha, izi zitha kubwezeretsedwanso ndi jakisoni wa morphine, cocaine, methamphetamine, nikotini, ndi ethanol kapena mwa kukumana ndi mavuto azachilengedwe ( Mueller ndi Stewart, 2000 ; Parker ndi Mcdonald, 2000 ; Wang et al., 2000 ; Li et al., 2002 ; Sanchez et al., 2003 ; Biala ndi Budzynska, 2006 ). Komanso, mofanana ndi kukhudzidwa, kubwezeretsanso mankhwala ndi jakisoni wa cocaine kapena amphetamine kumabwezeretsa morphine CPP kapena jakisoni wa morphine kumabwezeretsa nicotine CPP ( Do Ribeiro Couto et al., 2005 ; Biala ndi Budzynska, 2006 ).

C. Kuyanjana kwa Ubale pakati pa Kusalimbikitsa ndi Kubwereza

Pakati pa malingaliro omwe aperekedwa kuti afotokoze kubwereranso kwa mankhwala osokoneza bongo, lingaliro la chilimbikitso cha chilimbikitso limasonyeza kuti kugwiritsa ntchito mankhwala mobwerezabwereza kumabweretsa kulimba mtima kwakukulu kumalumikizidwa ndi mankhwala osokoneza bongo ndi zizindikiro zokhudzana ndi mankhwala osokoneza bongo, zomwe zikusonyeza kuti kukhudzidwa kungathandize kubwezeretsa khalidwe lofunafuna mankhwala osokoneza bongo ( Robinson ndi Berridge, 2003 ). Ngakhale kuti maphunziro omwe afotokozedwa pamwambapa akuoneka kuti akuchirikiza kwambiri mfundo imeneyi, kuyesa mwachindunji kwa lingaliro ili kwapereka zotsatira zosiyanasiyana. Chifukwa chake, pambuyo poti cocaine yatha, jakisoni wa cocaine kapena amphetamine, koma osati heroin, yabwezeretsa bwino kufunafuna cocaine. Ndikofunikira kudziwa kuti nyama zomwezi zophunzitsidwa cocaine zidawonetsanso kukhudzidwa kwa locomotor ku cocaine ndi amphetamine koma osati heroin ( De Vries et al., 1998b ). Nyama zophunzitsidwa kudzipatsa cocaine pansi pa njira yofikira nthawi yayitali (maola 6 patsiku) zawonetsa mayankho owonjezereka ofunafuna cocaine komanso locomotor ku vuto la cocaine poyerekeza ndi nyama zomwe sizingapezeke nthawi yayitali (ola limodzi patsiku) ( Ferrario et al., 2005 ). Mosiyana ndi zomwe zapezekazi, malipoti asonyeza kuti nyama zomwe zimalandira mankhwala kwa nthawi yayitali komanso kwa nthawi yochepa zimakhala ndi vuto la khalidwe la cocaine kapena heroin, koma nyama zomwe zimalandira mankhwala kwa nthawi yayitali zokha ndi zomwe zimalandira mankhwala kwa nthawi yayitali zomwe zimawonetsa kubwezeretsedwa kwa khalidwe la kufunafuna mankhwala osokoneza bongo poyankha jakisoni woyambitsa mankhwala osokoneza bongo ( Ahmed ndi Cador, 2006 ; Lenoir ndi Ahmed, 2007 ). Komabe, maphunzirowa adakhudza njira yobwezeretsanso mkati mwa gawo limodzi yokhala ndi nthawi ya kutha kwa mphindi 45, zomwe zingakhale zovuta chifukwa nyama zomwe zimalandira mankhwala kwa nthawi yayitali zimawonetsa kukana kwambiri kutha kwa mankhwala ( Ahmed et al., 2000 ). Kuphatikiza apo, Knackstedt ndi Kalivas (2007) anena kuti kuthekera kwa cocaine kuyambitsanso khalidwe la kufunafuna mankhwala osokoneza bongo sikudalira kukwera kwa khalidwe la kufunafuna mankhwala osokoneza bongo kapena kukhudzidwa ndi khalidwe. Ponseponse, deta ikuwonetsa kuti kukhudzidwa kumakula mpaka kuwonetsedwa mobwerezabwereza kwa mankhwala osokoneza bongo komwe kumachitika panthawi yodzipatsa mankhwala osokoneza bongo koma kukhudzidwa ndi locomotor sikumagwirizana nthawi zonse ndi kubwezeretsedwanso kwa khalidwe la kufunafuna mankhwala osokoneza bongo.

Kusowa kwa mgwirizano womveka bwino pakati pa kukhudzidwa kwa locomotor ndi kubwezeretsedwa kwa khalidwe lofunafuna mankhwala osokoneza bongo kungapangitse kukayikira kutsimikizika kwa chitsanzo chodziwitsira. Poganizira kutsimikizika kwa nkhope, kubwezeretsedwanso ndi chitsanzo chovomerezeka kuposa kudziwitsira, popeza nyama zimadzipatsa zokha mankhwalawo pomwe woyeserayo amapereka mankhwalawo mu chitsanzo chomaliza. Komabe, kutsimikizika kwa kapangidwe ka chitsanzo chobwezeretsa kwakayikiridwanso ( Epstein et al., 2006 ). Chifukwa chake, zifukwa zosiya kugwiritsa ntchito mankhwala osokoneza bongo, zochitika zomwe zimagwirizanitsidwa ndi kuyambitsidwa kwa kubwezeretsedwa, komanso nthawi yomwe chiwopsezo cha kubwezeretsedwa chimasiyana pakati pa nyama ndi anthu ( Epstein et al., 2006 ). Kuphatikiza apo, maphunziro obwezeretsa nthawi zambiri amaphatikizapo njira zowonongera zomwe sizofala kwa anthu ogwiritsa ntchito mankhwala osokoneza bongo ( Fuchs et al., 2006 ). Kuphatikiza pa kusiyana kwa njira yoperekera, kubwezeretsedwanso ndi kudziwitsira kumasiyana pa kuchuluka kwa mankhwala omwe nyama zimakumana nawo komanso kuthamanga komwe mankhwala amalowa nawo m'mitsempha yapakati. Ngakhale kuti mitundu yonse iwiri ili ndi zofooka, monga momwe tidzafotokozera pansipa, zikuwoneka kuti pali kugwirizana kwakukulu pakati pa njira zolumikizirana za mitsempha ya sensitization ya khalidwe ndi khalidwe lobwezeretsa kufunafuna mankhwala osokoneza bongo, zomwe zikusonyeza kuti chitsanzo cholumikizirana cha khalidwe chili ndi mphamvu yogwirizana ndi chitsanzo chobwezeretsanso. Chifukwa chake, munthu anganene kuti zotsatira zomwe zapezeka kuchokera ku maphunziro odziwitsa, makamaka, zitha kuwonetsa momwe mankhwala osokoneza bongo amakhudzira ntchito ya mitsempha yapakati. Kuphatikiza apo, kuthekera kulipo kuti sensitization ndi chinthu chimodzi chomwe chimapangitsa kuti munthu abwererenso kuchira. Pachifukwa ichi, lipoti laposachedwa likuwonetsa kuti zoyambitsa za cocaine zomwe zimayambitsa kulowererapo zitha kukhala ndi mphamvu zolimbikitsa zomwe zingathandize kubwezeretsanso kufunafuna mankhwala osokoneza bongo ( Keiflin et al., 2008 ). Pofufuza kusiyana komwe kuli m'mabuku, ziyenera kudziwika kuti sensitization ya chilimbikitso, osati kuyenda, ndikofunikira kwambiri pakuledzera ( Robinson ndi Berridge, 2008 ). Chifukwa chake, ndizotheka kuti ngakhale dera lamagetsi likhoza kufika pamlingo wapamwamba kwambiri wa sensitization, dera la chilimbikitso limapitilizabe kukulitsa. Pankhaniyi, nyama zomwe zimapeza nthawi yayitali zingasonyeze kuchuluka kofanana kwa mphamvu ya kuyenda koma kuchuluka kwa kubwezeretsanso khalidwe lofunafuna mankhwala osokoneza bongo.

III. Neurocircuitry

A. Neurons motsutsana ndi maulendo

Powerenga udindo wa malo osiyanasiyana a ubongo mu kulimbikitsa khalidwe kapena kubwezeretsanso, kuyesera kumadalira zipsinjo zazing'ono kapena zosatha kapena jekeseni wa agonists kapena otsutsa. Zotsatira za maphunzirowa zikhoza kumasuliridwa kuti ziwonetsedwe kuti ma neuroni akugwira ntchito m'madera amenewa mu makhalidwe omwe akuyang'aniridwa. Komabe, wina ayenera kukumbukira kuti zigawo za ubongo zinakambirana pansipa kuti zigwire ntchito yoyendetsa mayendedwe a mankhwala. Choncho, atatha kufotokoza deta yomwe ikuthandizira kapena kukana kuyika kwa madera ena a ubongo pakulimbikitsa kapena kubwezeretsanso, kukambirana za kuyanjana kwa madera osiyanasiyana a ubongo, pogwiritsa ntchito malumikizano odziwika bwino, amaperekedwa.

B. Kusokoneza

Pokambirana za ma neural circuits omwe amayambitsa sensitization, munthu ayenera kuganizira kuti yankho lowonjezera la motor-stimulant lili ndi magawo awiri osiyana: kuyambitsa ndi kufotokozera. Kutengera jakisoni wa amphetamine wamkati mwa mutu, poyamba zidatsimikizika kuti zochita za mankhwala pa VTA ndizo zimayambitsa kuyambitsa sensitization, pomwe zochita mkati mwa nucleus accumbens ndizo zimayambitsa kufotokozera sensitization ( Kalivas ndi Weber, 1988 ). Kafukufuku wa lesion nawonso wakhudza medial prefrontal cortex (mPFC) pakukula kwa sensitization ya khalidwe. Mwachitsanzo, zilonda za ibotenate za mPFC, zomwe zimaphatikizapo madera a prelimbic ndi infralimbic, zidasokoneza kuyambitsa kwa sensitization ku cocaine ndi amphetamine ( Wolf et al., 1995 ; Cador et al., 1999 ; Li et al., 1999 ). Kuphatikiza apo, zilonda zosiyana za dera la prelimbic la mPFC ndi excitotoxin quinolinic acid zinaletsanso kuyambitsa kwa sensitization yoyambitsidwa ndi cocaine ( Tzschentke ndi Schmidt, 1998 , 2000 ). Komabe, olemba omwewa adanenanso kuti zilonda zazikulu kapena zosiyana za mPFC quinolinic acid sizinasinthe kuyambitsa kwa sensitization ku amphetamine, zomwe zikusonyeza kuti pali kusiyana pakati pa sensitization yoyambitsidwa ndi cocaine ndi amphetamine ( Tzschentke ndi Schmidt, 2000 ).

Kuwonjezera pa dongosolo la mesocorticolimbic (monga, VTA, nucleus accumbens, ndi mPFC) ventral pallidum, hippocampus, amygdala, laterodorsal tegmentum (LDT), ndi paraventricular nucleus (PVN) ya thalamus zanenedwa kuti zimagwira ntchito pakukula kwa sensitization. Motero, kafukufuku wa lesion adawonetsa kuti LDT ndi PVN, koma osati hippocampus, zimagwira ntchito pakukula kwa sensitization ( Wolf et al., 1995 ; Young ndi Deutch, 1998 ; Nelson et al., 2007 ). Komabe, zoyeserera zina zidawonetsa kuti kuletsa kwa dorsal koma osati ventral hippocampus kunaletsa kuwonetsedwa kwa sensitization ya amphetamine ( Degoulet et al., 2008 ). Mosiyana ndi zomwe zapezekazi, kafukufuku waposachedwa adawonetsa kuti sensitization ya amphetamine imadalira ntchito yowonjezera ya ventral hippocampal neurons yomwe imawonjezera ntchito ya VTA dopamine neurons ( Lodge and Grace, 2008 ). Zilonda za Ibotenate za amygdala zanenedwa kuti zimatseka kapena sizikhudza kukula kwa sensitization ya amphetamine ( Wolf et al., 1995 ; Cador et al., 1999 ). Pomaliza, maphunziro ndi μ-opioid agonists ndi antagonists akusonyeza kuti ventral palladium imakhudzidwa poyambitsa ndi kuwonetsa sensitization ya khalidwe ku morphine ( Mickiewicz et al., 2009 ). Monga momwe tidzafotokozera pansipa, ndizotheka kuti gawo lililonse la ubongo limakhudza chitukuko cha sensitization pokhudza dongosolo la mesocorticolimbic dopamine.

Ma circuit odziwika bwino a khalidwe labwino amaphatikizapo ma dopamine projections kuchokera ku VTA kupita ku nucleus accumbens ndi ma glutamate projections kuchokera ku mPFC kupita ku nucleus accumbens ( Pierce ndi Kalivas, 1997a ). Kuwonjezera pa dopamine, ma GABAergic neurons amatuluka kuchokera ku VTA kupita ku nucleus accumbens ndi mPFC, pomwe ma dopamine terminals omwe ali mu nucleus accumbens amatulutsanso glutamate ( Van Bockstaele ndi Pickel, 1995 ; Tecuapetla et al., 2010 ). Kuphatikiza apo, dera ili likhoza kuyatsidwa ndi ma projections kuchokera ku mPFC kupita ku VTA ( Li et al., 1999 ), mwina kudzera mu LDT ( Omelchenko ndi Sesack, 2005 , 2007 ). Kuwonjezera pa kulumikizana mwachindunji, VTA mwina imakhudza mwachindunji ma nucleus accumbens ndi mPFC kudzera mu ma projections kupita ku basolateral amygdala ndi PVN ( Oades ndi Halliday, 1987 ; Kita ndi Kitai, 1990 ; Takada et al., 1990 ; Shinonaga et al., 1994 ; Moga et al., 1995 ). Pomaliza, hippocampus ikhoza kukhudza dongosolo la dopamine la mesolimbic kudzera mu ma inputs ku VTA ( Lodge ndi Grace, 2008 ). Chifukwa chake, monga momwe zasonyezedwera mu Chithunzi 1 A, mPFC imapereka ma input oyambitsa, mwachindunji kapena mwanjira ina kudzera mu LDT, kupita ku VTA, yomwe imapereka mphamvu ya dopaminergic ku ma nucleus accumbens, mwachindunji kapena mwanjira ina kudzera mu basolateral amygdala ndi PVN. Dera ili likhozanso kukhudzidwa ndi ma input olunjika a hippocampal ku VTA ndi mPFC ku ma nucleus accumbens. Neurochemistry ndi neuropharmacology ya dera ili zidzakambidwa pansipa.

Chizindikiro cha 1. 

Onani ndemanga yayikulu: 

Chizindikiro cha 1. 

Kuyerekeza kwa neurocircuitry yomwe ikuphatikizidwa pakulimbikitsa ndi kubwezeretsa khalidwe. Nucleus accumbens (NAc) imatumizira kuti zitha kuyendetsa magalimoto. A, poyesa kudziwitsa, nucleus accumbens imayendetsedwa ndi dopamine zoperekedwa kuchokera ku VTA kuti imakhala yosasunthika kapena ikuchita mwachindunji kudzera mwa PVN ndi abygdala (BLA). Nucleus accumbens imathandizanso kulumikizana mwachindunji kuchokera ku mPFC komanso ndondomeko yosagwirizana ndi LDT / PPT ndi VTA. Potsirizira pake, VTA imalandira kulandira kwa glutamate kuchokera ku hippocampus (Hip). B, malo oyang'anizana ndi kubwezeretsedwa ndi ofanana ndi omwe akuthandizira kupatula ngati Hip imagwira dera kudzera ku NAc m'malo mwa VTA.

C. Kubwerera / Kubwezeretsanso

Kafukufuku wofufuza za neurocircuitry ya kubwezeretsedwa kwa khalidwe lofunafuna mankhwala amachitiranso kuyeza kwa Fos kaphatikizidwe pogwiritsa ntchito mankhwala osokoneza bongo, kugonana, kapena kupanikizika maganizo kapena kugwiritsira ntchito mankhwala osokoneza bongo kapena kusinthidwa kosinthika kwazomwe mukufuna kusankha kuti musinthe. Kukongola kwa Cocaine kumaphatikizapo Fos kaphatikizidwe mu VTA, pakati, ndi pakatikati pa amygdala, pamene kuyimba kwachisomo kumabweretsa kuwonjezereka kwa Fos mu nucleus accumbens, basolateral amygdala, ndi hippocampus, ndipo cocaine ndi cue kuyamikira kudachulukitsa Fos mu anterior cingulate kolera (Neisewander et al., 2000). Kukanika kwa VTA, nucleus accumbens core, ventral pallidum, ndi kuvomereza mPFC zonse zimapewa kubwezeretsedwa kwa cocaineMcFarland ndi Kalivas, 2001; Capriles et al., 2003). Kuwonjezera apo, jekeseni wa cocaine m'kati mwa mPFC kapena morphine mu VTA imabwezeretsanso khalidwe lofunafuna mankhwala osokoneza bongo (Stewart, 1984; Park et al., 2002). Kuwonjezera pa zigawo zomwe takambirana ndi kubwezeretsedwa kwa mankhwala osokoneza bongo (Capriles et al., 2003; McLaughlin ndi See, 2003; Fuchs et al., 2004; McFarland et al., 2004; Chaudhri et al., 2008), amygdala yamtunduwu imaphatikizapo kubwezeretsedwa kwa cocaine - ndi khalidwe lofuna heroin (Meil ndi See, 1997; Kruzich ndi See, 2001; Fuchs ndi See, 2002; Kantak et al., 2002; McLaughlin ndi See, 2003), pamene hippocampus yachinyengo ndi yachinyama yakhala ikuphatikizidwa mu chikhalidwe-ndi kudalira kubwezeretsedwa, mwachindunji (Sun ndi Rebec, 2003; Fuchs et al., 2005). Potsirizira pake, PVN yakhala ikukhudzidwa ndi kubwezeretsedwa kwadongosolo-kukakamiza mowa (Hamlin et al., 2009). Zigawo za ubongo zomwe zimasonyezedwa kuti zimakhudzidwa ndi kupanikizika zimaphatikizapo nucleus accumbens shell, pakati pa amygdala, pakati pa bedi la stria terminalalis, ndi m'mbuyo mwa zigawo zomwe zatchulidwa kale kuti zibwezeretsedwe mankhwala osokoneza bongo (Shaham et al., 2000a,b; McFarland et al., 2004). Kuwonjezera pa zigawo zomwe takambiranapo, LDT ndi pedunculopontine tegmentum (PPT) posachedwapa zawonetsedwa kuti zikuphatikizidwanso ndi mankhwala osokoneza bongo, ngakhale kuti ntchito yawo kupsinjika-ndi kubwezeretsa kubweretsanso sikuyenera kufufuzidwa (Schmidt et al., 2009). Choncho, ngakhale kuti dera lapadera lokhazikitsiranso liripo, nkhawa, cues, ndi nkhani zimakhudza oyendetsa maguluwa kudzera muzipangizo zina.

Kafukufuku wakale akusonyeza kuti dera lobwezeretsa limaphatikizapo dera laling'ono la mota ndi dera laling'ono la limbic ( Kalivas ndi McFarland, 2003 ). Gawo laling'ono la mota ndi chiwonetsero kuchokera ku dorsal mPFC kupita pakati pa nucleus accumbens, chomwe chikuganiziridwa kuti ndi njira yomaliza yobwezeretsa. Monga momwe zasonyezedwera mu Chithunzi 1 B, dera laling'ono la limbic lili ndi VTA, basolateral amygdala, LDT/PPT, hippocampus, ndi amygdala yowonjezereka, yomwe imaphatikizapo chipolopolo cha nucleus accumbens, central nucleus ya amygdala, ndi bedi nucleus ya stria terminalis. Monga tafotokozera kale, kubwezeretsanso kufunafuna mankhwala nthawi zambiri kumaphatikizapo kupatsa nyama mankhwala, cue, kapena stress, ndi madera enaake a neuroanatomical a dera laling'ono la limbic subcircuit subserve iliyonse mwa mitundu iyi ya kubwezeretsanso. Motero, mPFC imapita ku VTA mwachindunji kapena kudzera mu LDT/PPT ndipo, pankhani ya kupsinjika, kudzera mu amygdala yowonjezereka ( Shaham et al., 2000b ; Kalivas ndi McFarland, 2003 ; McFarland et al., 2004 ; Schmidt et al., 2009 ). VTA imabwerera ku mPFC ya dorsal mwachindunji, kapena pankhani ya zizindikiro, kudzera mu amygdala ya basolateral, ( Kalivas ndi McFarland, 2003 ). Pomaliza, hippocampus ya dorsal ndi PVN zimapereka chidziwitso chazomwe zikuchitika ku limbic circuit mwa kukhudza basolateral amygdala ndi nucleus accumbens shell, motsatana ( Fuchs et al., 2007 ; Hamlin et al., 2009 ). Komabe, ziyenera kudziwika kuti mabuku ambiri okhudza neurocircuitry of reinstatement amachokera ku maphunziro a cocaine. Lipoti laposachedwa lofufuza za ma neural circuits a khalidwe lofunafuna heroin latsimikizira kwambiri zomwe zapezeka ndi cocaine koma linasonyeza kuti pali ma circuits owonjezereka obwezeretsanso heroin kudzilamulira yokha ( Rogers et al., 2008 ). Monga momwe zilili ndi sensitization, kukambirana za neurochemistry ndi neuropharmacology of reinstatement kwaperekedwa mu gawo IV.

D. Neural Circuitry Maubwenzi pakati pa Sensitization ndi Kubwerera

Zikuonekeratu mu Chithunzi 1 kuti pali kugwirizana kwakukulu m'magawo omwe amakhudzidwa ndi machitidwe olimbikitsa ndi kubwezeretsa mphamvu. Dongosolo la mesocorticolimbic dopamine likuwoneka ngati dera loyambirira, mPFC ikupita ku VTA kudzera mu LDT/PPT, yomwe kenako imapita ku nucleus accumbens. Mapulojekiti ochokera ku mPFC mwachindunji kupita ku nucleus accumbens nawonso ndi ofala pakubwezeretsa mphamvu ndi kukulitsa mphamvu. PVN ndi basolateral amygdala zimatha kugwira ntchito ngati malo olumikizirana pakati pa VTA ndi nucleus accumbens. Kuphatikizidwa kwa hippocampus kumawoneka kuti kumasiyana pamitundu iwiriyi, pomwe kulowetsa ku chipolopolo cha nucleus accumbens ndikofunikira pakubwezeretsa mphamvu ndi kulowetsa ku VTA ndikofunikira pakukulitsa mphamvu. Mfundo zingapo zofunika ziyenera kudziwika ponena za maphunziro omwe amatsimikizira magawo omwe amakhudzidwa ndi khalidwe loyambitsidwa ndi mankhwala. Choyamba, maphunziro ambiri okhudza kukulitsa mphamvu ya khalidwe amakhudza zilonda asanayambe kugwiritsidwa ntchito ndi mankhwala (mwachitsanzo, panthawi yoyambitsa neuroplasticity yoyambitsidwa ndi mankhwala), pomwe maphunziro okhudza kubwezeretsanso mphamvu amakhudza njira zomwe zinachitika pambuyo pa mbiri ya kumwa mankhwala (mwachitsanzo, panthawi yowonetsa neuroadaptations yoyambitsidwa ndi mankhwala). Chachiwiri, maphunziro okhudza kukhudzidwa kwa ubongo sanapeze magawo ang'onoang'ono omwe angathandize kukhudzidwa kwa ubongo chifukwa cha momwe zinthu zilili kapena kukhudzidwa kwa ubongo chifukwa cha kugwiritsa ntchito mankhwala osokoneza bongo. Komabe, pali kuyanjana kwakukulu m'magawo a mitsempha omwe amakhulupirira kuti ndi omwe amachititsa kuti munthu asamavutike ndi khalidwe lake komanso kubwezeretsanso khalidwe lofunafuna mankhwala osokoneza bongo. Deta iyi imapereka chitsimikizo chowonjezera cha chitsanzo cha kukhudzidwa kwa ubongo chifukwa imawoneka kuti ikuneneratu molondola momwe ubongo umagwiritsira ntchito mankhwala osokoneza bongo. Chifukwa chake, ndizotheka kuti kuwonetsedwa mobwerezabwereza kwa magawo omwe afotokozedwa pamwambapa ndi mankhwala osokoneza bongo, kaya ndi okhazikika kapena osakhazikika, kumabweretsa kusintha komwe kungayambitse kubwereranso kufunafuna mankhwala osokoneza bongo.

IV. Neurochemistry / Neuropharmacology

A. Kusokoneza

1. Dopamine.

Kafukufuku oyambirira amasonyeza kuti kupititsa patsogolo dopamine kupititsa patsogolo njira zochepetsera mphamvu zowonjezera. Motero, malipoti amasonyeza kuti kutulutsa kwa dopamine kwa cocaine kunamuthandizidwa kapena kosasinthika mu VTA ya zinyama zozizwitsa (Kalivas ndi Duffy, 1993; Parsons ndi Justice, 1993). Komabe, dopamine neuron excitability imalimbikitsidwa mu VTA mwa zinyama zomwe zimapezeka mobwerezabwereza ndi amphetamine, cocaine, kapena ethanol (White ndi Wang, 1984; Henry et al., 1989; Brodie, 2002). Nyama zimakhudzidwa ndi cocaine, amphetamine, nicotine, kapena morphine (Robinson et al., 1988; Kalivas ndi Duffy, 1990; Johnson ndi Glick, 1993; Parsons ndi Justice, 1993; Shoaib et al., 1994), koma osati mowa (Zapata et al., 2006), akuwonetseratu kutulutsidwa kwa dopamine mu nucleus accumbens pofuna kuthana ndi vuto la mankhwala. Kuphatikiza pa dera lamakono, kafukufuku waposachedwa wagwira ntchito ya mesocortical dopamine. Kafukufuku wambiri wachitidwa ndi cocaine ndipo asonyeza kuti kayendedwe ka cocaine mobwerezabwereza kamapanga kusintha kwa nthawi pa mPFC dopamine transmission, kutuluka koyambirira kukugwirizana ndi kuchepa kwa mankhwala a cocaine-mediated dopamine ndipo kuchotsa nthawi yaitali kumagwirizanitsa ndi kupititsa patsogolo dopamine (Sorg et al., 1997; Chefer et al., 2000; Wu et al., 2003; Williams ndi Steketee, 2005). Amphetamine-yomwe inachititsa kuti anthu azikhala ndi mphamvu zowonongeka, amapezeka kuti sagwirizanitsidwa ndi kusintha kwa mPFC dopamine kutuluka pakapita nthawi yochepa, koma kuyezetsa nthawi yaitali sikunayambe (Peleg-Raibstein ndi Feldon, 2008). Mosiyana ndi zomwe zapezazi, kasamalidwe ka nicotine kowonjezera kumapangitsa kuti nicotine isatulutse dopamine mu mPFC 24 h pambuyo pa chithandizo cha tsiku ndi tsiku (Nisell et al., 1996). Kuphatikizidwa pamodzi, deta imeneyi imasonyeza kuti, makamaka, kudzikweza kwa khalidwe kumakhudzana ndi kutuluka kwa dopamine m'matumbo a mesocorticolimbic dopamine. Komabe, ziyenera kukumbukira kuti kafukufuku m'mabwinja a anthu komanso osakhala aumunthu amasonyeza kuti kuchepetsa kapena kutengeka kwa dopamine kumasulidwa kumachitika mwa anthu omwe amagwiritsidwa ntchito ndi cocaine kapena anyani omwe amaphunzitsidwa kudzipatsa okha mankhwala a cocaine (poyang'ana, onani Bradberry, 2007). Izi zikhoza kusonyeza kusiyana pakati poti anthu ndi zitsanzo za primate zimaphatikizapo kudya kocaini mochuluka kusiyana ndi mayesero a rodent omwe atchulidwa pamwambapa. Kuonjezerapo, pamene maphunziro a primate ndi anthu amaphatikizapo kugwiritsa ntchito mankhwala osokoneza bongo, maphunziro a ndondomeko amakhala makamaka osagwiritsidwa ntchito mankhwala osokoneza bongo, ngakhale kuti kafukufuku wofufuza vuto la cocaine mu makoswe ophunzitsidwa kudzipangira cocaine amapeza kutulutsidwa kwa dopamine mofanana ndi khalidwe lowonjezereka labwino (Hooks et al., 1994). Mosiyana ndi zomwe zapeza, anthu odzipereka omwe analandira katemera wosapitirira ana a amphetamine mu ma laboratori omwe anawonetseratu dopamine kumasulidwa mu nucleus accumbens chifukwa cha vuto la amphetamine ma sabata a 2 ndi chaka cha 1 poyerekeza ndi kuchepa [11C] kumanga raclopride (Boileau et al., 2006). Kuonjezera apo, lipoti la posachedwapa linasonyeza kuti mwa ogwiritsa ntchito mankhwala osokoneza bongo a cocaine, kayendedwe ka cocaine ka intranasal kanachulukitsa dopamine kumasulidwa mu ventral striatum (Cox et al., 2009). Mosiyana ndi maphunziro apitalo mwa anthu ndi anthu osakhala achibadwidwe, mankhwala a cocaine omwe anatulutsa dopamine ankachitidwa pamaso pa zida zogwiritsira ntchito mankhwala osokoneza bongo (Cox et al., 2009). N'zochititsa chidwi kuti mlingo wa dopamine womasulidwa unali wogwirizana kwambiri ndi mbiri ya ntchito ya psychostimulant, kutanthauza kuti kulimbikitsidwa kwa dopamine pogwiritsidwa ntchito mobwerezabwereza kwa mankhwala osokoneza bongo (Cox et al., 2009).

2. Dopamine Receptors.

Kuwonjezera pa kusintha kwa kutulutsidwa kwa ma neurotransmitter, kulumikizidwa kwa dopamine ku ma receptor ake kumachita gawo lofunika kwambiri pakulimbikitsa khalidwe. Mwachitsanzo, kuwonjezereka kwa kusangalala kwa ma neuron a dopamine a VTA komwe kumachitika ndi cocaine wobwerezabwereza kumalumikizidwa ndi kuchepa kwa dopamine D2 autoreceptor sensitivity ( White ndi Wang, 1984 ; Henry et al., 1989 ). Kuphatikiza apo, jakisoni wobwerezabwereza wa intra-VTA wa mlingo wochepa wa D2 antagonist eticlopride, womwe mwina umasankha autoreceptor, womwe umawonjezera mayankho olimbikitsa pambuyo pake ku amphetamine ( Tanabe et al., 2004 ). Kutsekedwa kwa dopamine D1 receptors mu VTA panthawi yoyambitsa kumalepheretsa kukula kwa amphetamine koma osati cocaine sensitization ( Stewart ndi Vezina, 1989 ; Vezina, 1996 ; Steketee, 1998 ). Kuphatikiza apo, jakisoni wobwerezabwereza wa 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H -3-benzazepine (SKF38393), agonist wa receptor wa D1, mu VTA adayambitsa chidwi cha cocaine ( Pierce et al., 1996b ). Ponseponse, deta iyi ikuwonetsa kuti kuchepa kwa kuletsa kwa ma neuron a dopamine mu VTA kumalola kukulitsa dopamine ya ma receptors a D1 m'derali omwe amatha kuwonjezera kutulutsidwa kwa glutamate motero kuyambitsanso ma neuron owonetsa dopamine ( Kalivas ndi Duffy, 1995 ; Wolf ndi Xue, 1998 ).

Mu nucleus accumbens, cocaine wobwerezabwereza wawonetsedwa kuti akuwonjezera mphamvu ya dopamine D1 receptor sensitivity ( Henry and White, 1991 ). Kuphatikiza apo, jakisoni wa (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1 H- benzazepine (SKF82958), dopamine D1 receptor agonist, mu nucleus accumbens pamodzi ndi systemic cocaine, adakulitsa kukula kwa mphamvu ya cocaine sensitivity ( De Vries et al., 1998a ). Kafukufuku wakale wasonyeza kuti jakisoni wa (±)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine hydrobromide (SKF81297) kapena SKF38393 mu mPFC adaletsa kutulutsa kwa cocaine kapena amphetamine sensitization ( Sorg et al., 2001 ; Moro et al., 2007 ), pomwe maphunziro ena sanapeze zotsatira zake ( Beyer ndi Steketee, 2002 ). Kuthekera kwa intra-mPFC quinpirole, agonist wa D2, kuletsa ntchito yoyendetsa thupi yomwe imachitika chifukwa cha cocaine kunachepa m'zinyama zomwe zimakhudzidwa ndi cocaine, pomwe jakisoni wobwerezabwereza wa D2 antagonist sulpiride mu mPFC yomwe imayambitsa cocaine sensitization ( Beyer ndi Steketee, 2002 ; Steketee ndi Walsh, 2005 ). Ngakhale kuti ntchito ya mPFC dopamine D1 receptors pa sensitization ikadali yofunikira kufotokozedwa bwino, deta yomwe ili pamwambapa ikusonyeza kuti ntchito ya dopamine D2 receptor mu mPFC yachepa, zomwe zikuthandizidwa ndi maphunziro ena ( Bowers et al., 2004 ).

3. Glutamate.

Malipoti oyamba adawonetsa kuti mu nyama zomwe zimakhudzidwa ndi amphetamine kapena cocaine, ma dopamine neurons mu VTA anali ndi mphamvu yoyankha kwambiri ku glutamate, zomwe zidaphatikizapo kuwonjezeka kwa α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor sensitivity ( White et al., 1995b ; Zhang et al., 1997 ). Kafukufuku wa microdialysis wavumbulutsa kuti kupereka amphetamine kwakanthawi kochepa kumapangitsa kuwonjezeka kwa glutamate mu VTA komwe sikuwonjezeka chifukwa chowonetsedwa mobwerezabwereza, pomwe cocaine imawonjezera glutamate mu VTA yokha ya nyama zomwe zimakhudzidwa ( Kalivas ndi Duffy, 1998 ; Wolf ndi Xue, 1998 ). Zilonda za Ibotenate za mPFC zimaletsa amphetamine kukweza glutamate mu VTA ( Wolf ndi Xue, 1999 ). Kuphatikiza apo, kubayidwa mobwerezabwereza kwa glutamate uptake inhibitor l- trans -pyrollidine-2,4-dicarboxylic acid mu VTA kunapangitsa kuti amphetamine isamayende bwino, zomwe zinalepheretsedwa ndi N -methyl-d-aspartate (NMDA) receptor antagonist 3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid ( Aked et al., 2005 ). Chifukwa chake, kuwonjezeka mobwerezabwereza kwa glutamate mu VTA kumawoneka kuti kumatha kuyambitsa kuyankha kwa khalidwe ku amphetamine kapena cocaine. Zotsatirazi zikugwirizana ndi zomwe zapezeka kuti kubayidwa mobwerezabwereza kwa amphetamine kapena morphine mu VTA kumayambitsanso kukhudzidwa ( Vezina et al., 1987 ; Kalivas ndi Weber, 1988 ).

Kafukufuku wam'mbuyo wamakono akuwonetsa kuti kusagwirizana ndi mankhwala osokoneza bongo, kuphatikizapo cocaine, amphetamine, ethanol, morphine, ndi nicotine, zimapangitsa kuti anthu omwe ali ndi kachilombo ka VMA,Ungless et al., 2001; Saal et al., 2003; Borgland et al., 2004). Pulogalamuyi, yomwe imadalira kuchitidwa kwa dopamine D1 receptors, ndi yaifupi pokhapokha patatha kayendedwe ka cocaine koma imatenga osachepera miyezi ya 3 pambuyo pa cocaine kudzilamulira (Saal et al., 2003; Schilström et al., 2006; Chen et al., 2008). Kafukufuku wowonjezera wasonyeza kuti LTP yophatikizidwa ndi cocaine mu VTA chifukwa cha kulembedwa kwa mapulogalamu a AMPA omwe alibe GluR2 subunit, yomwe imapangitsa kuwonjezeka Ca2+ Kuperewera kwa mapulogalamu awa (Bellone ndi Lüscher, 2005; Mameli et al., 2007; Argilli et al., 2008). Kupsinjika maganizo, komwe kumadziwika kuti kudandaulirana ndi mankhwala osokoneza bongo (Kalivas ndi Stewart, 1991), imathandizanso LTP ku VTA dopamine neurons (Saal et al., 2003). Chinthu cha Corticotropin-release factor (CRF), chomwe chimasulidwa mu VTA poyankha kupsinjika (Wang et al., 2005), ikhoza kuyambitsa mauthenga ovomerezeka a NMDA, ndipo zowonjezerekazi zimapangidwira m'magulu okhala ndi mbiri yobwerezabwereza ya cocaine (Hahn et al., 2009). N'zochititsa chidwi kuti CRF ikhoza kutumiza kachilombo koyambitsa AMPA muzilombo mobwerezabwereza kupezeka ku cocaine koma osati nyama za cocaineHahn et al., 2009). Zimayesedwa kuti mayankho owonjezereka a AMPA receptors kwa CRF amapanga kutulukira kwa dopamine kutuluka mu mesocorticolimbic dopamine system (Ungless et al., 2010). Potsirizira pake, kusungunula kwa VTA dopamine neurons kungathandizidwe kwambiri ndi kuonongeka kwa CRF chifukwa cha kuchepetsa kupopera kwa dopamine D2 ndi mapepala a GABA-B (Beckstead et al., 2009). Kuphatikizidwa pamodzi, deta imeneyi imapereka chikhalidwe cha thupi kuti likhale ndi mauthenga otchuka a mesocorticolimbic dopamine ogwirizana ndi kuwonetsa khalidwe ndi kulimbikitsa kugwiritsa ntchito mankhwala osokoneza bongo komanso kupsinjika maganizo.

Mosiyana ndi VTA, cocaine wobwerezabwereza amachepetsa, m'malo mowonjezera, kuyankha kwa mitsempha ku glutamate mu nucleus accumbens ( White et al., 1995a ). Kuzindikira khalidwe la cocaine kumagwirizanitsidwa ndi kuchepa kwa glutamate mu nucleus accumbens, pomwe jakisoni wa cocaine kapena amphetamine wovuta amachititsa kuti glutamate ituluke m'derali ( Pierce et al., 1996a ; Reid ndi Berger, 1996 ; Baker et al., 2002 ; Kim et al., 2005 ). N'zodziwikiratu kuti lipoti lina linasonyeza kuti kuwonjezeka kwa cocaine mu nucleus accumbens glutamate release kumachitika kokha mwa nyama zomwe zinayamba kukhudzidwa ( Pierce et al., 1996a ). Kuphatikiza apo, kubwezeretsedwa kwa glutamate ya basal ndi N -acetylcysteine ​​kunaletsa kuwonetsa khalidwe ( Madayag et al., 2007 ). Motero kuchepa kwa glutamate ya basal yomwe imapezeka m'zinyama zomwe zimakhudzidwa kumawoneka kuti kumalola kutulutsidwa kwa glutamate poyankha vuto la mankhwala osokoneza bongo komanso kuwonetsa kukhudzidwa ( Xi et al., 2002 ). Kafukufuku wowonjezera wasonyeza kuti nyama zomwe zachotsedwa ku cocaine mobwerezabwereza zimasonyeza kuwonjezeka kwa AMPA/NMDA receptor ratio mu nucleus accumbens, zomwe zikusonyeza LTP ( Kourrich et al., 2007 ). N'zofunika kudziwa kuti pakayesedwa ndi cocaine kuti aone ngati ikukhudzidwa, nyama zimawonetsa kuchepa kwa AMPA/NMDA receptor ratio patatha maola 24, zomwe zikusonyeza kuti nthawi yayitali nucleus accumbens neurons imakhala ndi vuto la kukhumudwa ( Thomas et al., 2001 ; Kourrich et al., 2007 ). Ponseponse, deta iyi ikusonyeza kuthekera kwa kuchepa kwa glutamate m'magazi kumabweretsa LTP state yomwe imasinthidwa ndi kutulutsidwa kwa glutamate komwe kumachitika chifukwa cha cocaine ( Thomas et al., 2008 ).

Monga VTA, ma neuron mu mPFC amasonyeza kuyankha kwakukulu ku glutamate atatha kukhudzana ndi amphetamine mobwerezabwereza ( Peterson et al., 2000 ). Kuphatikiza apo, K + -kuyambitsa glutamate efflux mu mPFC kunawonjezeka mwa nyama atatha kukhudzana ndi methamphetamine mobwerezabwereza ( Stephans ndi Yamamoto, 1995 ). Cocaine yobwerezabwereza inawonetsedwa kuti imapangitsa kuwonjezeka kwa mPFC glutamate yomwe imayendetsedwa ndi cocaine, kuchotsedwa kwakanthawi (koma osati kwakanthawi) kuchokera ku cocaine mobwerezabwereza komwe kumalumikizidwa ndi kuwonjezeka kwa cocaine mu kuchuluka kwa glutamate yakunja kwa mPFC ( Williams ndi Steketee, 2004 ). Ndizofunikira kudziwa kuti, monga momwe zidawonedwera kale mu nucleus accumbens ( Pierce et al., 1996a ), cocaine idangowonjezera kuchuluka kwa glutamate ya mPFC mwa nyama zomwe zidawonetsa kukhudzidwa kwa khalidwe ku cocaine ( Williams ndi Steketee, 2004 ). Deta iyi imasiyana ndi zomwe zidachokera ku kafukufuku wakale, momwe jakisoni wa cocaine wovuta sanakhudze kuchuluka kwa glutamate ya mPFC mwa nyama zomwe zimakhudzidwa ( Hotsenpiller ndi Wolf, 2002 ). Pomaliza, maphunziro a thupi akuwonetsa kuti cocaine yobwerezabwereza imayambitsa LTP mu mPFC yomwe imadalira dopamine D1 receptors ndipo imachokera ku kuchepa kwa GABA-A receptor-mediated inhibition ya pyramidal neurons ( Huang et al., 2007a ). Kawirikawiri, detayi ikuchirikiza lingaliro lakuti kufalikira kwa glutamate mu mPFC kumagwirizanitsidwa ndi kukhudzidwa kwa khalidwe.

4. Othandizira a Glutamate.

Monga tafotokozera pamwambapa, kupititsa patsogolo kwa glutamate kwa VTA dopamine neurons yomwe imapezeka m'zinthu zowonongeka zimaphatikizapo mapulogalamu a AMPA (Zhang et al., 1997). Pochirikiza izi, jekeseni mobwerezabwereza wa AMPA mu VTA yomwe imayambitsa cocaine mphamvu (Dunn et al., 2005), pamene injini za intra-VTA AMPA m'zinthu zothandizira zimapangitsa kuti dopamine ndi glutamate zisulidwe mu nucleus accumbens ndi glutamate kumasulidwa mu VTA (Giorgetti et al., 2001). Zofufuza pa zotsatira za kubwereza mankhwala mobwerezabwereza pamagulu a magulu a AMPA mu VTA zakhala zikuphatikizidwa ndi kuchuluka kwa magulu a GluR1 kapena kusintha kwa GluRs (Fitzgerald et al., 1996; Churchill et al., 1999; Bardo et al., 2001; Lu et al., 2002). Kafukufuku watsopano posonyeza kuti cocaine mobwerezabwereza imalimbikitsa kuwonjezeka kwa GluR2-zopanda AMPA receptors mu VTA dopamine neurons, zomwe zimapangitsa kuti chiwerengero cha AMPA / NMDA chikhale chogwirizana ndi LTP (Bellone ndi Lüscher, 2005; Mameli et al., 2007; Argilli et al., 2008). Ponena za ovomerezeka a NMDA, kuyang'anira kwa mpikisano wokonda mpikisano wa NMDA wothandizira 3- (2-carboxy-piperazin-4-yl) -propyl-1-phosphonic acid ku VTA ndi systemic cocaine kapena VTA amphetamine amaletsa kukula kwa khalidwe lolimbikitsa (Kalivas ndi Alesdatter, 1993; Cador et al., 1999). Kujambulidwa kwadongosolo kwa antchito a NMDA omwe amasankha amtundu wa NMDA omwe ali ndi magulu a NR2 amalepheretsanso kukula kwa mphamvu ya cocaine komanso kuwonjezereka kwa cocaine ku AMPA / NMDA receptor ratios ku VTA (Schumann et al., 2009). Kuwonjezera apo, kulimbikitsidwa kwa cocaine kapena morphine kumagwirizanitsidwa ndi kuwonjezeka kwa mawonedwe a NMDA NR1 (Fitzgerald et al., 1996; Churchill et al., 1999). Pomaliza, jekeseni wa nonselective metabotropic glutamate receptor (mGluR) wotsutsa ku VTA amachititsa kuti amphetamine azidziwitsidwa, koma kubwereza mobwerezabwereza kwa agonist nonselective kugwilitsika kumatulutsa mphamvu ku cocaine (Kim ndi Vezina, 1998; Dunn et al., 2005).

Majekeseni a AMPA mu nucleus accumbens amapanga makina akuluakulu a nyama zamtundu wa cocaine poyerekeza ndi maulamuliro, pamene jekeseni wa AMPA wotsutsa 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo {f} quinoxaline-2,3-dione inaletsa chitukuko za kukakamizidwa kwa cocaine (Pierce et al., 1996a; Ghasemzadeh et al., 2003). Intra-accumbens dongosolo la 2 - [(1S,2S) -2-carboxycyclopropyl] -3- (9H-xanthen-9-yl) -d-alanine (LY341495), wotsutsana ndi gulu lachiwiri la GGM, amachititsa kuti anthu asamangoganizira bwino makoswe a amphetamine koma osati ndi makoswe (Chi et al., 2006). Kutchulidwa mobwerezabwereza ku cocaine, potsatira kuchotsedwa, kumapangitsa kuti magulu a GluR1 ndi AMPA awonongeke m'mwamba mkati mwa nucleus accumbens pambuyo pa kuchoka kwa nthawi yaitali, koma mobwerezabwereza amphetamine sichigwira ntchito m'mawu a pamwamba a AMPA (Churchill et al., 1999; Boudreau ndi Wolf, 2005; Boudreau et al., 2007; Boudreau et al., 2009; Ghasemzadeh et al., 2009b; Nelson et al., 2009; Schumann ndi Yaka, 2009). Kumbali inayi, ma subunits a NMDA amatha kuwonjezeka kapena kuchepa kwa nyama zowonongeka,Yamaguchi ndi al., 2002; Nelson et al., 2009; Schumann ndi Yaka, 2009). N'zochititsa chidwi kuti kuvutika maganizo kwa nthawi yaitali komwe kunayambitsidwa ndi vuto loyambitsa cocaine mu nyama zowonongeka zomwe zafotokozedwa mu gawo IV.A.3 zikufanana ndi kuchepa kwa mapepala a AMPA mumtundu wa nucleus accumbens (Thomas et al., 2001; Boudreau et al., 2007; Kourrich et al., 2007), yomwe imabwerera kumbuyo kwa tsamba la cocaine yomwe imapangidwira patsogolo pambuyo pa kuchotsa (Ferrario et al., 2010). Kuphatikizidwa pamodzi, deta imeneyi imasonyeza kuti kuyendetsa khalidwe kumagwirizanitsa ndi kupititsa patsogolo katemera wa glutamate kudzera m'makompyuta a AMPA mumtengowo womwe umatha kuchepetsedwa ndi magulu awiri a magulu. Pochirikiza mfundo yotsirizirayi, kayendedwe ka cocaine kawiri kawiri katsimikiziridwa kuchepetsa ntchito ya gulu la II mGluR ndi kufotokozera mu nucleus accumbens, zomwe zimalola kuti kumasulidwa kwa glutamate kuwonjezeke m'dera lino (Xi et al., 2002; Ghasemzadeh et al., 2009b). Kuphatikiza apo, dongosolo la kayendedwe ka (1R,4R,5S,6R) -4-amino-2-oxabicyclo [3.1.0] hexane-4,6-dicarboxylic acid (LY379268), gulu lachiŵiri la GGRR agonist, limateteza khunyu kowonjezereka kowonjezera kowonjezereka kowonongeka chifukwa cha vuto la amphetamine m'matenda a amphetamine komanso cocaine yowonjezera ubwino wotsogoleredwa yowoneka mu zinyama izi (Kim et al., 2005).

Kafukufuku wokhudza momwe mPFC glutamate receptors imagwirira ntchito wasonyeza kuti mphamvu ya gulu II mGluR agonist (2 R ,4 R )-4-aminopyrrolidine-2,4-dicarboxylate yoletsa kuwonetsa kwa khalidwe lodziwika bwino ikalowetsedwa m'derali imachepa pambuyo posiya cocaine kwa nthawi yayitali ( Xie ndi Steketee, 2009a ). Kuphatikiza apo, kulowetsedwa kwa LY341495, gulu II mGluR antagonist, kunawonjezera kufalikira kwa mesocorticolimbic glutamate m'manja koma osati makoswe omwe ali ndi cocaine, zomwe zikusonyeza kuti kuperekedwa mobwerezabwereza kwa cocaine kumachepetsa kuletsa kwa tonic kwa kufalikira kwa glutamate ( Xie ndi Steketee, 2009b ). Pothandizira izi, kuperekedwa mobwerezabwereza kwa cocaine kumachotsa ma mGluR a gulu II kuchokera ku mapuloteni awo a G mu mPFC ( Xi et al., 2002 ; Bowers et al., 2004 ). Kuphatikiza apo, cocaine mobwerezabwereza inachepetsa kupsinjika kwa nthawi yayitali kwa mGluR komwe kumachitika chifukwa cha gulu lachiwiri la mGluR mu mPFC ( Huang et al., 2007b ). Ponseponse, deta iyi ikusonyeza kuti kukhudzidwa kwa cocaine kwa nthawi yayitali kumalumikizidwa ndi kuchepa kwa ntchito ya mPFC gulu lachiwiri la mGluR. Pomaliza, kusiya cocaine mobwerezabwereza kwa nthawi yayitali kumalumikizidwa ndi kuwonjezeka kwa phosphorylation ya ma subunit a GluR1 komanso kuwonjezeka kwa malo a synaptic a AMPA ndi NMDA receptors ( Zhang et al., 2007 ; Ghasemzadeh et al., 2009a ). Pamodzi, kusintha kumeneku mu metabotropic ndi ionotropic receptors kungayembekezeredwe kuwonjezera kusangalala kwa ma neuron owonetsa mPFC.

Kukhudzidwa kwa glutamate m'madera ena a ubongo omwe amapanga dera lothandizira kukhudzidwa kwakhala kochepa. Kukhudzidwa kwa morphine kumagwirizanitsidwa ndi kuchepa kwa GluR2 mu amygdala ndi dorsal hippocampus popanda kusintha kwa GluR1 mu hippocampus ( Grignaschi et al., 2004 ; Sepehrizadeh et al., 2008 ). Izi zitha kupangitsa kuti ma receptor a AMPA omwe amalowa m'thupi achuluke chifukwa cha calcium omwe amaganiziridwa kuti ndi omwe amachititsa kuti synaptic plasticity ipangidwe. Kulowetsa AMPA mu LDT kumawonjezera glutamate mu VTA, yomwe imawonjezeka m'zinyama zomwe zimakhudzidwa ndi amphetamine ( Nelson et al., 2007 ). Chifukwa chake, glutamate, pamlingo wosiyanasiyana wa neural circuitry yomwe yafotokozedwa mu gawo lachitatu, ikuwoneka kuti ikukhudzidwa ndi chitukuko cha kukhudzidwa.

5. Chidule.

Monga momwe taonera Chith. 2B ndipo mwachidule Gulu 1, kubwerezedwa mobwerezabwereza ku mankhwala osokoneza bongo kumawonjezera kuwonjezereka kochepa mu somatodendritic dopamine kumasulidwa mu VTA (Kalivas ndi Duffy, 1993) chifukwa cha kuchepa kwa mphamvu ya autoreceptor (White ndi Wang, 1984; Henry et al., 1989), yomwe ingagwiritse ntchito pa mapepala a D1 opititsa patsogolo kutulutsidwa kwa glutamate ku mPFC kulumikiza mazati ndi kuyambitsa LTP mu dopamine neurons (Kalivas ndi Duffy, 1995; Ungless et al., 2001; Saal et al., 2003). Kuwonjezeka kwa kutulutsidwa kwa glutamate kumatha kuchita pa mapepala a AMPA kuti amalimbikitse dopamine kumasulidwa mu nucleus accumbens (Karreman et al., 1996; Ungless et al., 2010). Nthawi yayitali, nucleus accumbens dopamine kumasulidwa kumachitika chifukwa cha synaptic plasticity pa mlingo wa nucleus accumbens, makamaka mwa kuwonjezeka kwa ntchito ya calcium / calmodulin-dependent protein kinase II (Pierce ndi Kalivas, 1997b). Kupititsa patsogolo dopamine kumasulidwa mu nucleus accumbens kungagwiritse ntchito pa D1 receptors pofuna kulimbikitsa kudziletsa kwa khalidwe (Giorgetti et al., 2001). MPFC zowonongeka kwa VTA ndizolowera mwachindunji kapena zosalongosoka pogwiritsa ntchito glutamate kuchokera ku LDT (Omelchenko ndi Sesack, 2005, 2007; Nelson et al., 2007). Kuwonjezera pamenepo, mkati mwa mPFC, D2 ndi kagwiridwe ka gulu la mGluR kagulu kafupika (Beyer ndi Steketee, 2002; Bowers et al., 2004), kulola kuwonjezereka kwakukulu kwa maonekedwe a neurons. Mu nucleus accumbens, miyeso ya calutamate yayamba kuchepetsedwa, potero imayesa kulembetsa malamulo oyenera omasulidwa omwe amalimbikitsa kutulutsa mankhwala osokoneza bongo kuchokera ku mPFC neurons mu zinyama zolimbikitsa (Pierce et al., 1998; Baker et al., 2002; Xi et al., 2002). Mankhwala ochepa omwe amachepetsedwa amadzimadzi amakhulupirira kuti amalimbikitsa ntchito ya AMPA (Boudreau ndi Wolf, 2005; Boudreau et al., 2007; Kourrich et al., 2007). Kuchulukitsidwa kwa glutamate mu nucleus accumbens kungathe kuchita pa mapulogalamu awa opititsa patsogolo AMPA kuti alimbikitsenso kudziletsa kwa khalidwe (Pierce et al., 1996a; Ghasemzadeh et al., 2003). Pomalizira, maphunziro omwe amasonyeza kuti mobwerezabwereza cocaine amachititsa kuwonjezereka kwa calcium-permmeable receptors mu hippocampus ndi amygdala amasonyeza kuti kutsegula m'mimba mkati mwa misala ya misala kungathandizidwe kwambiri ndi mavitamini ku VTA ndi nucleus accumcums kuchokera ku hippocampus ndi amygdala, motero (Shinonaga et al., 1994; Lodge ndi Grace, 2008; Sepehrizadeh et al., 2008).

Chizindikiro cha 2. 

Onani ndemanga yayikulu: 

Chizindikiro cha 2. 

A, neurochemistry ndi neuropharmacology ya maulendo othandizira ndi kubwezeretsa poyerekeza ndi maulendo achilendo. B, kulimbikitsidwa kumagwirizanitsa ndi kupititsa patsogolo dopamine kutengera kuchokera ku VTA mpaka ku nucleus accumbens zomwe zimachokera ku kuchepetsedwa kwa D2 autoreceptor ntchito ndi kupititsa patsogolo ntchito ya AMPA (A). Matenda opangidwa kuchokera ku mPFC kupita ku nucleus accumbens ndi VTA amapezedwanso mu zinyama zowonongeka ndipo amalingalira kuti zimapangitsa mbali yochepetsetsa yochepetsetsa yofalitsidwa ndi D2 receptors ndi gulu la II mGluRs (mG2 / 3). Kuwonjezera apo, kuchepa kwa ntchito ya cystine / glutamate antiporter (X) kumapangitsa kuti m'malo otsika kwambiri a glutamate muzitsulo zomwe zimapangitsa kuti chiwerengero cha AMPA chisamveke m'derali. Pomalizira, kuchepa kwa glutamate kumatulutsa kuchepetsedwa kwa gulu la II mGluRs mu nucleus accumbens zomwe zingathandize kuti kutuluka kwa glutamate kuwonjezeke mu dera lino (osati kufotokozedwa). Monga chidziwitso (C), kubwezeretsedwa kumagwirizananso ndi miyeso yochepetsetsa ya glutamate mu nucleus accumbens ndi kuwonjezeka kwa mapulogalamu a AMPA m'maderawa pamodzi ndi kumasulidwa kwa glutamate komwe kumatulutsa mankhwala. Kaya kusintha kwina kosokoneza bongo kumawoneka polimbikitsanso kumawonekera pobwezeretsedwa sikudziwika.

Onani gome ili: 

MASAMBA 1 

Chidule cha kusintha kosokonekera kwa mankhwala komwe kumakhudzana ndi kulimbikitsa khalidwe ndi kubwezeretsanso

Onani malemba oyenera.

B. Kubwezeretsanso

1. Dopamine.

Zofukufuku pa ntchito ya dopamine kubwezeretsanso kwa khalidwe lofunafuna mankhwala adayang'ana makamaka pa nucleus accumbens ndipo atulutsa zotsatira zosiyana. Motero, cocaine- kapena amphetamine-primed reinstatement ikugwirizana ndi kuchepetsedwa (Neisewander et al., 1996) kapena kupititsidwa patsogolo (Ranaldi et al., 1999; Di Ciano et al., 2001) dopamine kumasulidwa mu nucleus accumbens. Majekeseni a Intra-accumbens a amphetamine, omwe amachititsa kuti dopamine zisulidwe, awonedwa kuti abwezeretsanso khalidwe la ethanol (Samson ndi al., 1999). Kubwezeretsanso chifukwa cha khalidwe la amphetamine kapena la ethanol likufuna kusasinthika kapena kuchepetsedwa kwa dopamine, motero (Katner ndi Weiss, 1999; Di Ciano et al., 2001). Zonse ziwiri za D1 ndi D2 mu nucleus accumbens zikuwoneka kuti zimathandizira kubwezeretsa khalidwe, ngakhale kuti zotsatira sizikhala zogwirizana nthawi zonse. Kupweteka kwa (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390) mkati mwa nucleus accumbens amachepetsa cocaine-primed reinstatement ya cocaine kufunafuna kapena kubwezeretsedwanso kwa mpweya wa ethanol (Anderson et al., 2003; Bachtell et al., 2005; Chaudhri et al., 2009; Madayag et al., 2010). Mosiyana, intra-accumbens SKF81297 imabwezeretsanso khalidwe la cocaine (Bachtell et al., 2005; Schmidt et al., 2006). Zotsatira zomwezo zakhala zikudziwika kwa obvomerezeka a D2. Choncho, intra-accumbens quinpirole kapena 7-hydroxy-2-dipropylaminotetralin imabwezeretsa khalidwe la cocaine, pamene eticlopride kapena sulpiride imalepheretsa kubwezeretsedwa kwa cocaine (Bachtell et al., 2005; Anderson et al., 2006; Schmidt et al., 2006). Ngakhale kuti chiwerengerocho chikuwoneka kuti chimawonetsa kuti ntchito yaikulu ya nucleus accumbens dopamine receptors mu kubwezeretsanso, kusagwirizana kumawonjezereka podziŵika kwake kwa chipolopolo (Anderson et al., 2003, 2006; Schmidt et al., 2006) motsutsana ndi maziko (McFarland ndi Kalivas, 2001; Bachtell et al., 2005; Madayag et al., 2010). Choncho, ngakhale kuti D1 yotsutsana ndi microinjection mu chipolopolo imaletsa cocaine kubwezeretsa kufunafuna, chithandizo chofanana chomwecho ndichosafunikira.

Kuwonjezera pa nucleus accumbens, malipoti ena awonetsanso kuti machitidwe ena a dopamine ali ndi khalidwe lobwezeretsa. Kulowetsa kwa dopamine antagonist fluphenazine mu dorsal mPFC kunaletsa kubwezeretsanso kwa cocaine- kapena stress-primed, pomwe jakisoni wa dopamine restored cocaine ( McFarland ndi Kalivas, 2001 ; McFarland et al., 2004 ). SCH23390 mu dorsal mPFC imaletsa kubwezeretsanso kwa cocaine- kapena heroin-primed kufunafuna mankhwala osokoneza bongo ndi cocaine- ndi stress-primed kubwezeretsanso kwa CPP ( Sanchez et al., 2003 ; Sun ndi Rebec, 2005 ; Onani, 2009 ). Intra-mPFC microinjection ya D1 agonist SKF81297 inapangitsa kubwezeretsanso kwa cocaine-primed kufunafuna ( Schmidt et al., 2009 ). Komanso, intra-mPFC microinjection ya D2 antagonist eticlopride inachepetsa kubwezeretsanso kwa cocaine-primed kufunafuna mankhwala osokoneza bongo ( Sun ndi Rebec, 2005 ). Kubwezeretsanso khalidwe lofunafuna cocaine kumagwirizanitsidwa ndi kutulutsidwa kwa dopamine komwe kumayendetsedwa ndi cocaine mu amygdala ( Tran-Nguyen et al., 1998 ). Kulowetsa amphetamine mu basolateral amygdala komwe kumalimbikitsidwa ndi cue-induced reinstalation, pomwe SCH23390 yoperekedwa kudera lomweli idaletsa kubwezeretsedwanso kwa cue-ndi cocaine-induced kwa cocaine-induced ( Onani et al., 2001 ; Ledford et al., 2003 ; Alleweireldt et al., 2006 ). Ponseponse, deta ikuwonetsa kuti kukondoweza kwa dopamine kwa ma D1 receptors (mu mPFC, nucleus accumbens shell, ndi amygdala) ndi ma D2 receptors (mu nucleus accumbens) kumatha kusintha kubwezeretsedwa kwa khalidwe lofunafuna mankhwala osokoneza bongo.

2. Glutamate.

Mofanana ndi dopamine, maphunziro ochuluka omwe adachitapo kanthu pokhudzana ndi kugwiritsidwa ntchito kwa glutamate mu kubwezeretsedwa kwa kufunafuna mankhwala akuyang'ana pa nucleus accumbens. Kuwonetsedwa kowonjezereka kwa cocaine kumachepetsa miyeso ya basal glutamate mumtundu wa core accumcums core, yomwe, ikabwezeredwa ku machitidwe ovomerezeka ndi pretreatment with N-acetylcysteine, imaletsa kubwezeretsedwa kwa cocaine kufunafuna (Baker et al., 2003). Kupweteka kwa (S) -4-carboxyphenylglycine, yomwe imaletsa cystine / glutamate antiporter, mkati mwa nucleus accumbens maziko amachititsa zochita za N-acetylcysteine ​​(Kau et al., 2008). Kubwezeretsedwa kwa Cocaine kumaphatikizidwa ndi kuwonjezeka kwa glutamate pakati pa nucleus accumbens zomwe zingaletsedwe ndi kutsegula kwa mPFC (McFarland et al., 2003). Zotsatira zomwezo zakhala zikufotokozedwa kwa heroin ndi kubwezeretsedwa-kubweretsedwanso kwa heroin kufunafuna khalidwe (LaLumiere ndi Kalivas, 2008). Majekeseni a AMPA pachimake kapena chipolopolo cha nucleus accumbens akhoza kubwezeretsa cocaine kufuna, zotsatira zomwe zingatsekezedwe ndi jekeseni wa zitsimikizo kwa GluR1 subunit m'madera omwewo (Cornish et al., 1999; Ping et al., 2008). Cocaine self-administration imapangitsa kuwonjezeka kwa maonekedwe a GluR2-akusowa AMPA receptors mu nkhono zomwe zimaphatikizidwa ndi neurons, zomwe zingathe kubweretsa boma la LTP, monga zikuwonetsedwa ndi maphunziro a thupi (Conrad et al., 2008; Mameli et al., 2009; Moussawi et al., 2009). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) pachimake kapena chipolopolo chimalepheretsa cocaine-, heroin, kapena kubwezeretsedwanso (Chimanga ndi Kalivas, 2000; Park et al., 2002; Bäckström ndi Hyytiä, 2007; Wotchuka ndi al., 2008; LaLumiere ndi Kalivas, 2008). Kusokonezeka kwa kugulitsa magulu a GluR2 ku membrane pachimake kapena chipolopolo amalepheretsanso kubwezeretsedwa kwa cocaine -Wotchuka ndi al., 2008). Ndizodabwitsa kuti, monga kutsimikiziridwa, zizindikiro zochepetsetsa zimachepetsanso AMPA pamasom'pamaso pamtundu wa 24 h pambuyo poyang'ana pa izi (Conrad et al., 2008). Mosiyana ndi zowonjezereka zokhudzana ndi nucleus accumbens AMPA receptors ndi kubwezeretsa, jekeseni wa NMDA agonist 1-aminocyclobutane-CIS-1,3-dicarboxylic acid mkatikati mwabwezeretsa cocaine kufunafuna, koma jekeseni wa 2-amino-5-phosphonovaleric asidi, wotsutsana ndi NMDA, mkati mwake kapena chipolopolo chimakhala chopanda mphamvu, kapena kubwezeretsa cocaine kufunafuna (Cornish et al., 1999; Chimanga ndi Kalivas, 2000; Bäckström ndi Hyytiä, 2007; Wotchuka ndi al., 2007). Pomalizira, jekeseni wa gulu la II mGluR agonist LY379268 mu nucleus accumbens limateteza 1) chifukwa cha heroin kufunafuna ndi 2) kufunafuna mankhwala osokoneza bongo (cocaine)Bossert et al., 2006; Peters ndi Kalivas, 2006). Pamodzi, ma datawa amasonyeza kuti cocaine kudziyendetsa bwino amachepetsa mchere wa basaltutate mu nucleus accumbens zomwe zimachepetsanso gulu la II mGluR kusindikizidwa kwa glutamate (Moran et al., 2005), motero kuonjezera kutuluka kwa glutamate ndi kukakamizidwa kwotsatira kwa mapemphero a AMPA omwe amalimbikitsa kubwezeretsedwa. Magulu ochepa omwe amapezeka a glutamate amathetsedwa ndi kuwonjezeka kwakumvetsera kwa AMPA receptors zomwe zingasinthidwe panthawi yobwezeretsedwa (Conrad et al., 2008; Mameli et al., 2009; Moussawi et al., 2009). Zotsatirazi zikhoza kutetezedwa ndi normalizing basal glutamate, kuyambitsa gulu la II mGluRs, kapena kutseka receptors AMPA (Chimanga ndi Kalivas, 2000; Park et al., 2002; Bossert et al., 2006; Peters ndi Kalivas, 2006; Bäckström ndi Hyytiä, 2007; Wotchuka ndi al., 2008; Kau et al., 2008; LaLumiere ndi Kalivas, 2008).

Kuwonjezera pa nucleus accumbens, kafukufuku wasonyeza kuti kutseka ma ionotropic receptors okhala ndi kynurenic acid kapena CNQX mu VTA kumaletsa kubwezeretsedwanso kwa cocaine, pomwe jakisoni wa LY379268 amaletsa kufunafuna heroin komwe kumachitika chifukwa cha context ( Bossert et al., 2004 ; Sun et al., 2005 ; Schmidt et al., 2009 ). CNQX mu LDT/PPT yanenedwanso kuti imaletsa khalidwe lofunafuna cocaine ( Schmidt et al., 2009 ). MGluR1 agonist (3,4-dihydro-2 H- pyrano[2,3- b ]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone (JNJ16259685) mu dorsal hippocampus imaletsa kubwezeretsedwanso kwa cocaine komwe kumadalira context ( Xie et al., 2010 ). Mosiyana ndi zimenezi, CNQX kapena 2-amino-5-phosphonovaleric acid mu basolateral amygdala sizimasokoneza kufunafuna cocaine yomwe imayambitsa cue ( Onani et al., 2001 ). Motero, kuletsa kufalikira kwa glutamate mu VTA kapena dorsal hippocampus, koma osati basolateral amygdala, sikungakhudze kufunafuna mankhwala obwezeretsedwa. Pomaliza, infralimbic AMPA yoperekedwa imaletsa kufunafuna cocaine mwa kuyambitsa infralimbic-cortex-to-nucleus-accumbens shell circuit panthawi yotha ( Peters et al., 2008 ). Izi zikusonyeza kuti kuyambitsa kwa derali kumathandiza kuphunzira kuletsa khalidwe lofunafuna mankhwala pamene mankhwala sakupezekanso.

3. Chidule

Monga taonera Chith. 2C ndipo mwachidule Gulu 1, kubwezeretsa kumaphatikizapo kupititsa patsogolo kuthamanga kwa glutamate kuchokera kumtundu wa mPFC mpaka pamtunda wa phokoso la accumuls limene limakhalapo chifukwa cha kuchepa kwa glutamate mu nucleus accumbens zomwe zimapangitsa kuchepetsa kutulutsa mphamvu ya glutamate kutulutsa ndipo motero kuwonjezeka kwa mankhwala osokoneza bongo omwe amachititsa kuti AMPA receptors (Cornish et al., 1999; Chimanga ndi Kalivas, 2000; Baker et al., 2003; McFarland et al., 2003; Moran et al., 2005; Bäckström ndi Hyytiä, 2007; Wotchuka ndi al., 2008; LaLumiere ndi Kalivas, 2008). Amalandira awa AMPA awonetsedwa kuti awonjezeka ntchito yomwe yachepetsedwa mwa kuwonetsedwa ndi zida zapakati pa mankhwala osokoneza bongo (Conrad et al., 2008). MPFC imakhudzanso kubwezeretsedwanso kudzera mu malingaliro a glutamatergic kwa LDT / PPT ndi VTA pogwiritsa ntchito mapulogalamu a AMPA m'madera awiriwa (Schmidt et al., 2009). Dopamine zowonongeka kuchokera ku VTA kupita ku nucleus accumbens, mPFC, ndi amygdala zotsatizana zikuwoneka kuti zikuphatikizidwa kubwezeretsanso. Mwachindunji, dopamine yogwiritsira ntchito D1 receptors ikhoza kukondweretsa glutamate projection neurons mu amygdala ndi mPFC (Onani ndi al., 2001; Sun ndi Rebec, 2005; Alleweireldt et al., 2006; Schmidt et al., 2009; Onani, 2009), pamene dopamine ikugwira ntchito pa D1 ndi D2 receptors mu nucleus accumbens shell (Anderson et al., 2003; Bachtell et al., 2005; Anderson et al., 2006; Schmidt et al., 2006) angagwirizane ndi mapepala a AMPA kuchepetsa kutumiza kwa GABAergic ku palralum, yomwe yasonyezedwa kuti ndi yofunikira kubwezeretsanso (O'Connor, 2001; Torregrossa et al., 2008).

C. Neurochemical / Neuropharmacological Ubale pakati pa Kusalimbikitsa ndi Kubwereza

Zofanana zambiri zimawoneka poyerekeza ndi matenda a neurochemistry ndi neuropharmacology ya chidziwitso cha khalidwe ndi kubwerera. M'magwiri onse awiriwa, mazenera a glutamate m'munsimu amachepetsedwa (Baker et al., 2002, 2003) koma kubwereranso kwa mankhwala kumawonjezera glutamate m'dera lino (Pierce et al., 1996a; Moran et al., 2005), zomwe zingathe kuchitapo kanthu pa mapepala a AMPA pofuna kulimbikitsa kuyankha kwa khalidwe (Pierce et al., 1996a; Cornish et al., 1999). Zonsezi zotsutsana ndi mankhwala osokoneza bongo zimapangitsa LTP mu nucleus accumbens neurons yomwe imaphatikizapo kulowetsedwa kwa GluR2-zoperewera AMPA receptors mu membrane, zomwe zingasinthidwe mwadzidzidzi ndi kubwereranso kwa mankhwala kapena mankhwala ophatikizana ndi mankhwala (Thomas et al., 2001; Boudreau ndi Wolf, 2005; Boudreau et al., 2007; Kourrich et al., 2007; Conrad et al., 2008; Mameli et al., 2009; Moussawi et al., 2009; Ferrario et al., 2010). Kuwonongeka kapena kuchepetsedwa kwa thandizo la glutamate kuchokera ku mPFC kupita ku nucleus accumbens kumateteza mawu akulimbikitsa ndi kubwezeretsa (Pierce et al., 1998; McFarland et al., 2003). Kuonjezera apo, mPFC zowonongeka kwa VTA kudzera pa LDT / PPT zomwe zimachitidwa pa mapemphero a AMPA zasonyezedwanso kukhala zofunika kwa mayankho onse a khalidwe (Nelson et al., 2007; Schmidt et al., 2009). Ngakhale kuti ntchito ya glutamate kubwezeretsanso ndi kuwonetsetsa zikuoneka kuti ikuwonekera, udindo wa dopamine machitidwe sali. Mwachitsanzo, kulimbikitsa, koma kusabwezeretsanso, kumagwirizanitsa ndi kuchepa kwachidziwitso ku mphamvu ya autoreceptor mu VTA yomwe imalola, mwa mbali, kuti ikhale yowonjezereka ya dopamine neurons (White ndi Wang, 1984; Henry et al., 1989). Komabe, mayankho a VTA a dopamine mobwerezabwereza a cocaine amawoneka kuti akuyambitsa chiyambi osati kuti mawu akulimbikitsa. Kuonjezera apo, ngakhale kuti jekeseni wa agonist wa D1 mu mPFC unayambitsanso khalidwe lofuna kukonda cocaine, sizinapangitse kuwonetsetsa (Beyer ndi Steketee, 2002; Schmidt et al., 2009). Kuphatikizidwa pamodzi, deta imasonyeza kuti maulendo a glutamate ndiwo ofunika kwambiri poyanjanitsa ndi kubwezeretsedwa. Kuwonjezera apo, deta imeneyi ikuwonetsa kufunika kokhala ndi chitsanzo chobwezeretsanso pofuna kutsimikizira kufunika kofufuza kuchokera ku khalidwe lolimbikitsa anthu kuti azibwezeretsa mankhwala.

V. Udindo wa Kusamalitsa pa Kubwereranso ku Mchitidwe Wofuna Kugwiritsa Ntchito Mankhwala Osokoneza Bongo

Ma neurocircuitry omwe amayambitsa kukhudzidwa kwa khalidwe ndi kubwereranso ku khalidwe lofunafuna mankhwala osokoneza bongo ndi ofanana, monga momwe zilili ndi njira zama neurochemical ndi neuropharmacological. Komabe, kafukufuku sanatsimikizire kuti kukhudzidwa kwa khalidwe kumachita gawo pakubwezeretsedwanso. Chifukwa chake, mankhwala omwe angabwezeretse kufunafuna mankhwala mwa nyama zomwe zachotsedwa ku kudzipangira cocaine awonetsedwanso kuti amabweretsa mayankho okhudzidwa mwa nyama zomwezi, pomwe mankhwala omwe sayambitsa kubwezeretsedwanso samabweretsa kukhudzidwa ( De Vries et al., 1998b , 2002 ). Maphunziro ena ayerekeza momwe kubwezeretsedwanso kwa mankhwala osavuta kugwiritsa ntchito poyerekeza ndi mankhwala osavuta kugwiritsa ntchito omwe ali ndi zotsatira zosiyanasiyana ( Ferrario et al., 2005 ; Ahmed ndi Cador, 2006 ; Knackstedt ndi Kalivas, 2007 ; Lenoir ndi Ahmed, 2007 ). Chifukwa chake, nyama zomwe zimalandira cocaine nthawi yayitali zimawonjezera kumwa kwawo cocaine ndikuwonetsa kuyankha kolimba kwambiri pobwezeretsedwera poyerekeza ndi nyama zomwe zimalandira cocaine nthawi yayitali, koma kusiyana kwa kukhudzidwa kwa khalidwe sikumawonekera nthawi zonse. N'zotheka kuti kusowa kusiyana kwa kukhudzidwa ndi khalidwe kungachitike chifukwa cha zotsatirapo zake. Chifukwa chake, kugwiritsa ntchito njira yophunzitsira yomwe imachepetsa kuchuluka kwa kuwonetsedwa kwa mankhwala osokoneza bongo musanayesedwe kuti mumve kapena mubwezeretsedwe kungalole munthu kudziwa ngati kukhudzidwa kumagwira ntchito pakubwezeretsedwe. Pachifukwa ichi, kafukufuku wakale adawonetsa kuti amphetamine yomwe idaperekedwa kale ndi woyeserera yomwe idapanga kukhudzidwa ndi khalidwe sikunangowonjezera mphamvu ya cocaine komanso kubwezeretsedwa komwe kumachitika chifukwa cha kuperekedwa kwa AMPA mkati mwa intra-accumbens ( Suto et al., 2004 ). Mu kafukufuku womwewo, zidawonetsedwa kuti kusiya nthawi yayitali kugwiritsa ntchito cocaine, kusiyana pakati pa nyama zomwe zimakhudzidwa ndi amphetamine ndi zowongolera sikunawonekerenso. Ponseponse, deta iyi ikuwonetsa kuti anthu omwe ali ndi kukhudzidwa ndi khalidwe [kukhudzidwa ndi khalidwe kotereku kungachitike chifukwa cha majini kapena kuwonetsedwa ndi zinthu zomwe zimasokoneza chilengedwe ( Altman et al., 1996 ) kapena omwe ali ndi mbiri yochepa yogwiritsa ntchito mankhwala osokoneza bongo] angakhale pachiwopsezo chobwereranso kufunafuna mankhwala osokoneza bongo. Chifukwa chake, kukhudzidwa ndi khalidwe kungakhale ndi gawo pakubwezeretsedwedwenso kumayambiriro kwa kugwiritsa ntchito mankhwala osokoneza bongo. Ndi kugwiritsa ntchito mankhwala osokoneza bongo kwa nthawi yayitali, mosasamala kanthu kuti njira yofikira kwakanthawi kapena yayitali imagwiritsidwa ntchito, zinthu zina, monga zoyambitsa za cocaine kukhala zoyambitsa tsankho, zitha kuthandizira kubwezeretsanso khalidwe kuposa zomwe zimapangidwa ndi kukhudzidwa ( Keiflin et al., 2008 ).

VI. Zotsatira Zothandizira

Ndemangayi ikukambirana za zoyesayesa zofufuza zomwe zavumbulutsa njira yolumikizirana mitsempha yomwe ikuwoneka kuti imayambitsa kukhudzidwa kwa khalidwe ndi kubwezeretsanso khalidwe lofunafuna mankhwala osokoneza bongo, makamaka m'machitidwe a makoswe. Kuphatikiza apo, deta yowunikira posachedwapa mu maphunziro a anthu, ngakhale kuti ndi yochepa, ikugwirizana kwambiri ndi kafukufuku wa nyama ( Koob ndi Volkow, 2010 ). Chifukwa chake, chilakolako choyambitsidwa ndi methylphenidate chomwe chimachitika mwa ogwiritsa ntchito cocaine molakwika pamaso pa zizindikiro, chimayambitsa madera a prefrontal cortical, kuphatikizapo orbital ndi medial prefrontal cortices ( Volkow et al., 2005 ). Kuphatikiza apo, kafukufuku wokhudza zithunzi wawonetsa kuti zizindikiro zimayambitsa hippocampus ndi amygdala mwa ogwiritsa ntchito mankhwala osokoneza bongo odziwa bwino ntchito ( Grant et al., 1996 ; Childress et al., 1999 ; Kilts et al., 2001 ; Volkow et al., 2004 ). Popeza kufunika kwa kusintha kwa machitidwe a glutamate mu machitidwe olimbikitsa ndi kubwezeretsa mphamvu (onani pamwambapa), kufufuza kwina kwa ma neurocircuitry omwe amachititsa kubwereranso kwa anthu omwe amagwiritsa ntchito mankhwala osokoneza bongo akuyembekezera kupangidwa kwa ma ligand oyenera a machitidwe a glutamate ( Koob ndi Volkow, 2010 ).

Ngakhale kuti maphunziro a khalidwe sanatsimikizire bwino momwe munthu amamvera akabwerera ku khalidwe lofunafuna mankhwala osokoneza bongo, zoyeserera zasonyeza kugwirizana kwakukulu mu mitsempha yamagazi. Chifukwa chake, popereka njira yoyesera yothandiza kwambiri, kuzindikira kumatha kukhala chitsanzo chothandiza kudziwa njira zomwe mobwerezabwereza mankhwala osokoneza bongo amasinthira ntchito ya ubongo kuti awonjezere mayankho a khalidwe ku mankhwala osokoneza bongo. Zotsatira zabwino za maphunzirowa zikatsimikiziridwa mu maphunziro obwezeretsa omwe amawononga nthawi yambiri komanso ovuta kwambiri. Mwachitsanzo, maphunziro okhudza kuzindikira adavumbulutsa kusowa kwa glutamate ya basal mu nucleus accumbens komwe kudatsimikiziridwa mwa nyama zomwe zidagwiritsa ntchito cocaine yokha. Izi zidapangitsa kuti zoyeserera ziwonetse kuti kubwezeretsa milingo ya basal glutamate mu nucleus accumbens kumatha kuchepetsa kubwereranso ku khalidwe lofunafuna mankhwala osokoneza bongo mwa mitundu ya nyama ndi anthu ( Baker et al., 2003 ; Mardikian et al., 2007 ; Zhou ndi Kalivas, 2008 ; Knackstedt et al., 2009 , 2010 ; Sari et al., 2009 ). Mtundu uwu wa kupita patsogolo kuyambira pa maphunziro okhala ndi chidziwitso cha khalidwe kupita ku kutsimikizira pogwiritsa ntchito mitundu yobwezeretsanso kufunafuna mankhwala osokoneza bongo komanso kupita ku mayeso azachipatala ndikofunikira kwambiri kuganizira za zolinga zomwe zingatheke za mankhwala zomwe zapezeka kuchokera ku ma genomic ndi ma proteomic screens, zomwe sizipereka umboni woyambirira wokhudza kukhudzidwa kwa kusintha kwa mankhwala osokoneza bongo komwe kumabwera chifukwa cha mankhwala osokoneza bongo.

Kuvomereza

Ntchitoyi inathandizidwa ndi National Institutes of Health National Institute on Drug Abuse [Grant DA023215] (ku JDS) [Thandizo DA015369, DA012513, DA003906] (mpaka PWK).

Zopereka za Olemba

Analemba kapena anathandizira kulemba bukuli: Steketee ndi Kalivas.

Mawu a M'munsi

  • Nkhaniyi ikupezeka pa intaneti pa http://pharmrev.aspetjournals.org.

    onetsani: 10.1124 / pr.109.001933.

  • ↵ 1 Mafupikitsidwe:

    • AMPA
    • α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate
    • CNQX
    • 6-cyano-7-nitroquinoxaline-2,3-dione
    • CPP
    • malo okonda malo
    • CRF
    • chotsitsa cha corticotropin
    • GluR
    • glutamate receptor
    • JNJ16259685
    • (3,4-dihydro-2H-pyrano [2,3-b] quinolin-7-yl) - (cis-4-methoxycyclohexyl) -methanone
    • LDT
    • laterodorsal tegmentum
    • LTP
    • zotheka nthawi yaitali
    • LY341495
    • 2 - [(1S,2S) -2-carboxycyclopropyl] -3- (9H-xanthen-9-yl) -d-alanine
    • LY379268
    • (1R,4R,5S,6R) -4-amino-2-oxabicyclo [3.1.0] hexane-4,6-dicarboxylic acid
    • mGluR
    • metabotropic glutamate receptor
    • mPFC
    • mphalapala yamkati
    • NMDA
    • N-methyl-d-aspartate
    • PPT
    • pedunculopontine tegmentum
    • PVN
    • phokoso lamakono
    • SCH23390
    • (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
    • SKF 81297
    • (±)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
    • SKF38393
    • 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
    • SKF82958
    • (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine
    • VTA
    • malo amtunda.

Zothandizira

  1. ↵
    1. Ahmed SH,
    2. Cador M

    (2006) Kusokonezeka kwa maganizo a maganizo ochotsera matenda a cocaine. Neuropsychopharmacology 31: 563-571.

  2. ↵
    1. Ahmed SH,
    2. Walker JR,
    3. Koob GF

    (2000) Kuwonjezereka kosalekeza kuchitsimikizo chotenga heroin mu makoswe okhala ndi mbiri ya mankhwala ochuluka. Neuropsychopharmacology 22: 413-421.

  3. ↵
    1. Aked J,
    2. Coizet V,
    3. Clark D,
    4. Overton PG

    (2005) Kuloledwa kwapadera kwa katemera wa glutamate m'dera la ventral tegmental kumapangitsa kuti azidziwitsidwa ndi khalidwe la d-amphetamine. Neuroscience 134: 361-367.

  4. ↵
    1. Alleweireldt AT,
    2. Hobbs RJ,
    3. Taylor Taylor,
    4. Neisewander JL

    (2006) Zotsatira za SCH-23390 zimalowerera mu amygdala kapena pafupi ndi cortex ndi basal ganglia pa cocaine kufunafuna ndi kudzilamulira pa makoswe. Neuropsychopharmacology 31: 363-374.

  5. ↵
    1. Altman J,
    2. Everitt BJ,
    3. Glautier S,
    4. Markou A,
    5. Nutt D,
    6. Oretti R,
    7. Phillips GD,
    8. Robbins TW

    (1996) Zomwe zimayambitsa matenda, zokhudzana ndi chikhalidwe ndi zachipatala zokhudzana ndi mankhwala osokoneza bongo: ndemanga ndi ndemanga. Psychopharmacology (Berl) 125: 285-345.

  6. ↵
    1. Anagnostaras SG,
    2. Robinson TE

    (1996) Kuwopsyeza kwa maganizo omwe amachititsa kuti amphetamine asokonezeke. Behav Neurosci 110: 1397-1414.

  7. ↵
    1. Anderson SM,
    2. Bari AA,
    3. Pierce RC

    (2003) Kulamulira kwa D1-ngati dopamine wothandizira antchito SCH-23390 mkatikatikati mwachinthu chomwe chimapangitsa kuti cocaine isabwezeretsedwe kachitidwe kofuna mankhwala mu makoswe. Psychopharmacology (Berl) 168: 132-138.

  8. ↵
    1. Anderson SM,
    2. Schmidt HD,
    3. Pierce RC

    (2006) Kulamulira kwa D2 dopamine antptist antagonist sulpiride mu chipolopolo, koma osati maziko, a nucleus accumbens amachititsa kuti cocaine kubwezeretsedwa kubwezeretsedwa kwa mankhwala kufunafuna. Neuropsychopharmacology 31: 1452-1461.

  9. ↵
    1. Argilli E,
    2. Sibley DR,
    3. Malenka RC,
    4. England PM,
    5. Bonci A

    (2008) Njira ndi nthawi ya cocaine yomwe imapangitsa kuti nthawi yayitali ikhale yovuta. J Neurosci 28: 9092-9100.

  10. ↵
    1. Bachtell RK,
    2. Whisler K,
    3. Karani D,
    4. Kudzikonda DW

    (2005) Zotsatira za intra-nucleus accumbens shell dongosolo la dopamine agonist ndi otsutsa pa makhalidwe a cocaine-kutenga ndi cocaine makhalidwe pakalo. Psychopharmacology (Berl) 183: 41-53.

  11. ↵
    1. Bäckström P,
    2. Hyytiä P

    (2007) Kuphatikizidwa kwa AMPA / kainate, NMDA, ndi mGlu5 receptors mu nucleus accumbens pachimake mwa kubwezeretsedwa kwa cocaine kufunafuna makoswe. Psychopharmacology (Berl) 192: 571-580.

  12. ↵
    1. Baker DA,
    2. McFarland K,
    3. Nyanja RW,
    4. Shen H,
    5. Tang XC,
    6. Toda S,
    7. Kalivas PW

    (2003) Matenda osokoneza bongo m'magulu a cystine-glutamate amatha kusinthika. Nat Neurosci 6: 743-749.

  13. ↵
    1. Baker DA,
    2. Shen H,
    3. Kalivas PW

    (2002) Kusinthana kwa mphutsi / glutamate kumapangitsa kuti mitundu yambiri yambiri isamalidwe. Amino Acids 23: 161-162.

  14. ↵
    1. Bardo MT,
    2. Robinet PM,
    3. Mattingly BA,
    4. Margulies YES

    (2001) Zotsatira za 6-hydroxydopamine kapena mobwerezabwereza amphetamine mankhwala pa mesencephalic mRNA magulu a AMPA glutamate receptor subunits mu khola. Neurosci Lett 302: 133-136.

  15. ↵
    1. Beckstead MJ,
    2. Gantz SC,
    3. Ford CP,
    4. Stenzel-Poore MP,
    5. Phillips PE,
    6. Mark GP,
    7. Williams JT

    (2009) CRF yopititsa patsogolo njira yotumizira njira ya GIRK ku dopamine neurons. Neuropsychopharmacology 34: 1926-1935.

  16. ↵
    1. Bellone C,
    2. Lüscher C

    (2005) mGluRs imachititsa kuti munthu asokonezeke maganizo nthawi yaitali m'dera la ventral teptional lomwe limaphatikizapo kusintha kwa maulendo a AMPA receptors. Eur J Neurosci 21: 1280-1288.

  17. ↵
    1. Benwell ME,
    2. Balfour DJ

    (1992) Zotsatira za mankhwala ovuta komanso obwerezabwereza a nicotine pa nucleus accumbens dopamine ndi ntchito yogulitsa. Br J Pharmacol 105: 849-856.

  18. ↵
    1. Beyer CE,
    2. Stafford D,
    3. LeSage MG,
    4. Glowa JR,
    5. Steketee JD

    (2001) Kawirikawiri kutulukira kwa toluene yotsekemera kumapangitsa khalidwe ndi matenda a m'maganizo kuti awononge makoswe. Psychopharmacology (Berl) 154: 198-204.

  19. ↵
    1. Beyer CE,
    2. Steketee JD

    (2002) Kulimbikitsidwa kwa Cocaine: kusinthika kwa dopamine D2 receptors. Cereb Cortex 12: 526-535.

  20. ↵
    1. Biala G,
    2. Budzynska B

    (2006) Kubwezeretsanso malo okongoletsedwa ndi chikondwerero chifukwa cha mankhwala osokoneza bongo: zotsatira za otsutsa a calcium. Eur J Pharmacol 537: 85-93.

  21. ↵
    1. Boileau I,
    2. Dagher A,
    3. Leyton M,
    4. Gunn RN,
    5. Baker GB,
    6. Diksic M,
    7. Benkelfat C

    (2006) Kuwonetsa chidwi cha zinthu zolimbikitsa mwa anthu: kafukufuku wa [ 11 C] raclopride/positron emission tomography mwa amuna athanzi. Arch Gen Psychiatry 63:1386–1395.

  22. ↵
    1. Borgland SL,
    2. Malenka RC,
    3. Bonci A

    (2004) Kuopsa kokhazikika kwa cocaine chifukwa cha mphamvu ya synaptic m'dera la ventral tegmental: electrophysiological ndi khalidweal correlates mu makoswe. J Neurosci 24: 7482-7490.

  23. ↵
    1. Bossert JM,
    2. Liu SY,
    3. Lu L,
    4. Shaham Y

    (2004) Udindo wochita zowonongeka pamtundu wa glutamate m'zochitika zowonjezera kubwereza kwa heroin kufunafuna. J Neurosci 24: 10726-10730.

  24. ↵
    1. Bossert JM,
    2. Mitengo GC,
    3. Sheffler-Collins SI,
    4. Ghitza UE

    (2006) MgluR2 / 3 agonist LY379268 amavomereza nkhaniyo-komanso kusabweretsedwa kobwezeretsedwa kwa sucrose kufunafuna koma osati kutsitsimula kudzilamulira pa makoswe. Behav Ubongo Res 173: 148-152.

  25. ↵
    1. Boudreau AC,
    2. Ferrario CR,
    3. Glucksman MJ,
    4. Wolf ME

    (2009) Njira zowonetsera kayendedwe ndi mapuloteni othandizira mapuloteni A magawo okhudzana ndi khalidwe lachidziwitso kwa cocaine. J Neurochem 110: 363-377.

  26. ↵
    1. Boudreau AC,
    2. Reimers JM,
    3. Milovanovic M,
    4. Wolf ME

    (2007) Maselo a AMPA mapulogalamu a AMPA m'kati mwa khola akuwonjezeka pa nthawi ya cocaine kuchoka koma atangomaliza kutsutsana ndi vuto la cocaine pogwirizana ndi kusintha kwa mapuloteni otchedwa protein kinases. J Neurosci 27: 10621-10635.

  27. ↵
    1. Boudreau AC,
    2. Wolf ME

    (2005) Kulimbikitsidwa kwa khalidwe kuti mukhojeine kumagwirizanitsidwa ndi kuwonjezeka kwa pamwamba pa AMPA kukuwonetseratu pamwamba pa nucleus accumbens. J Neurosci 25: 9144-9151.

  28. ↵
    1. Bowers MS,
    2. McFarland K,
    3. Nyanja RW,
    4. Peterson YK,
    5. Lapish CC,
    6. Gregory ML,
    7. Lanier SM,
    8. Kalivas PW

    (2004) Wothandizira G protein signaling 3: mlonda wachitetezo cha cocaine kufunafuna mankhwala ndi mankhwala. Neuron 42: 269-281.

  29. ↵
    1. Bradberry CW

    (2007) Kulimbikitsa kwa Cocaine ndi dopamine kukhazikitsidwa kwa zotsatirazi mu makoswe, abulu, ndi anthu: malo ogwirizana, kusagwirizana, ndi zomwe zimakhudza kuledzera. Psychopharmacology (Berl) 191: 705-717.

  30. ↵
    1. Brodie MS

    (2002) Kuwonjezeka kwa mpweya wa ethanol wa dopaminergic neurons wa ventral tegmental m'dera pambuyo pa mankhwala osokoneza bongo. Mowa Wotulutsa Zakumwa za Mowa 26: 1024-1030.

  31. ↵
    1. Cadoni C,
    2. Pisanu A,
    3. Solinas M,
    4. Kupeza E,
    5. Di Chiara G

    (2001) Kulimbikitsanso khalidwe pambuyo pobwereza ku Delta 9-tetrahydrocannabinol ndi kuwonetsetsa kwambiri ndi morphine. Psychopharmacology (Berl) 158: 259-266.

  32. ↵
    1. Cador M,
    2. Bjijou Y,
    3. Cailhol S,
    4. Stinus L

    (1999) D-amphetamine-yomwe inachititsa kuti anthu azikhala ndi khalidwe labwino: Kutanthauzira kumalo amodzi omwe amachititsa kuti thupi likhale lopanda mphamvu. Neuroscience 94: 705-721.

  33. ↵
    1. Capriles N,
    2. Rodaros D,
    3. Sorge RE,
    4. Stewart J

    (2003) Udindo wamtundu wa correx m'maganizo komanso mowa wa cocaine wobwezeretsa cocaine kufunafuna makoswe. Psychopharmacology (Berl) 168: 66-74.

  34. ↵
    1. Chaudhri N,
    2. Sahuque LL,
    3. Yoyamba JJ,
    4. Janak PH

    (2008) Kubwezeretsa mpweya wa ethanol mu makoswe kumayendetsedwa ndi zochitika zachilengedwe ndipo zimafuna kuti phokoso likhale lolimba. Eur J Neurosci 28: 2288-2298.

  35. ↵
    1. Chaudhri N,
    2. Sahuque LL,
    3. Janak PH

    (2009) Ethanol kufunafuna kuyambitsidwa ndi chilengedwe. Psychopharmacology (Berl) 207: 303-314.

  36. ↵
    1. Chefer VI,
    2. Morón JA,
    3. Hope B,
    4. Rea W,
    5. Shippenberg TS

    (2000) Kappa-opioid receptor activation imalepheretsa kusintha mu mesocortical dopamine neurotransication yomwe imachitika pakupewa cocaine. Neuroscience 101: 619-627.

  37. ↵
    1. Chen BT,
    2. Bowers MS,
    3. Martin M,
    4. Chiyembekezo FW,
    5. Guillory AM,
    6. Carelli RM,
    7. Chou JK,
    8. Bonci A

    (2008) Cocaine koma osati mphotho yaumwini yokha kayendetsedwe ka mankhwala kapena mankhwala osakanikirana a cocaine amachititsa kukhalabe ndi LTP mu VTA. Neuron 59: 288-297.

  38. ↵
    1. Chi H,
    2. Jang JK,
    3. Kim JH,
    4. Vezina P

    (2006) blockade ya group II metabotropic glutamate receptors mu nucleus accumbens imatulutsa hyperlocomotion m'makola omwe kale anali amphetamine. Neuropharmacology 51: 986-992.

  39. ↵
    1. Chiamulera C,
    2. Borgo C,
    3. Falchetto S,
    4. Valerio E,
    5. Tessari M

    (1996) Kukonzanso kwa Nikotini kwa chikonga chodzilamulira pambuyo pakutha kwazitali. Psychopharmacology (Berl) 127: 102-107.

  40. ↵
    1. Childress AR,
    2. Mozley PD,
    3. McElgin W,
    4. Fitzgerald J,
    5. Reivich M,
    6. O'Brien CP

    (1999) Kutsegulitsa kwa limbic panthawi yomwe chilakole chomwe chimayambitsa chidwi cha cocaine. Am J Psychiatry 156: 11-18.

  41. ↵
    1. Churchill L,
    2. Swanson CJ,
    3. Urbina M,
    4. Kalivas PW

    (1999) obwereza cocaine alters glutamate receptor subunit magawo a nucleus accumbens ndi gawo lachigawo la makoswe omwe amalimbikitsa chidwi. J Neurochem 72: 2397-2403.

  42. ↵
    1. Conrad KL,
    2. Tseng KY,
    3. Uejima JL,
    4. Reimers JM,
    5. Heng LJ,
    6. Shaham Y,
    7. Marinelli M,
    8. Wolf ME

    (2008) Kukonzekera kwa accumbens GluR2-akusowa AMPA receptors amachititsa kuti makina a cocaine azilakalaka. Nature 454: 118-121.

  43. ↵
    1. Chijeremani JL,
    2. Duffy P,
    3. Kalivas PW

    (1999) Ntchito ya nyukiliya imaphatikizira kupatsanso mankhwala obwera chifukwa cha cocaine. Neuroscience 93: 1359-1367.

  44. ↵
    1. Chijeremani JL,
    2. Kalivas PW

    (2000) Kufalitsa kwa glutamate mu nyukiliya kumabweza m'miyeso ya cocaine. J Neurosci 20: RC89.

  45. ↵
    1. Cox SM,
    2. Benkelfat C,
    3. Dagher A,
    4. Delaney JS,
    5. Durand F,
    6. McKenzie SA,
    7. Kolivakis T,
    8. Casey KF,
    9. Leyton M

    (2009) Striatal dopamine amayankha makina amomwe amachititsa kuti anthu azigwiritsa ntchito pokhapokha ngati anthu ena akuchita. Biol Psychiatry 65: 846-850.

  46. ↵
    1. Crombag HS,
    2. Grimm JW,
    3. Shaham Y

    (2002) Zotsatira za dopamine receptor antagonists pakukonzanso cocaine wofunikanso ndikudziwikanso pamalingaliro okhudzana ndi mankhwala. Neuropsychopharmacology 27: 1006-1015.

  47. ↵
    1. Cunningham CL,
    2. Olemekezeka D

    (1992) Chikhalidwe chotsatiridwa chotsogoleredwa ndi ethanol: chofunika pakulimbikitsanso malo okonda malo. Pharmacol Biochem Behav 43: 307-313.

  48. ↵
    1. De Vries TJ,
    2. Amatsuka AR,
    3. Shippenberg TS

    (1998a) Kulowetsedwa kwa D-1 receptor agonist mu nucleus accumbens kumapangitsa cocaine-induced behavioral sensitization. Neuroreport 9: 1763-1768.

  49. ↵
    1. De Vries TJ,
    2. Schoffelmeer AN,
    3. Binnekade R,
    4. Mulder AH,
    5. Vanderschuren LJ

    (1998b) Kubwezeretsedwa kwa mankhwala osokoneza bongo wa khalidwe la heroin-ndi cocaine pambuyo pa kutha kwa nthawi yaitali kumagwirizanitsidwa ndi kuwonetsa khalidwe lolimbikitsa. Eur J Neurosci 10: 3565-3571.

  50. ↵
    1. De Vries TJ,
    2. Schoffelmeer AN,
    3. Binnekade R,
    4. Raasø H,
    5. Vanderschuren LJ

    (2002) Kubwerera ku cocaine - ndi khalidwe la heroin loyendetsedwa ndi dopamine D2 receptors ndi kudalira nthawi ndi kugwirizana ndi khalidwe lolimbikitsa. Neuropsychopharmacology 26: 18-26.

  51. ↵
    1. de Amanda H,
    2. Stewart J

    (1981) Kubwereranso kwa cocaine-reinforced kuyankha pakalo. Psychopharmacology (Berl) 75: 134-143.

  52. ↵
    1. de Amanda H,
    2. Stewart J

    (1983) Mankhwala osokoneza bongo amachititsa kuti heroin-reinforced responding pirato. Psychopharmacology (Berl) 79: 29-31.

  53. ↵
    1. Degoulet M,
    2. Rouillon C,
    3. Rostain JC,
    4. David HN,
    5. Abraini JH

    (2008) Kutanthauzira kwa mawu osokoneza bongo, koma osati chithunzithunzi, hippocampus cha maonekedwe a chidziwitso kwa amphetamine. Int J Neuropsychopharmacol 11: 497-508.

  54. ↵
    1. Di Ciano P,
    2. Blaha CD,
    3. Phillips AG

    (2001) Kusintha kwa dopamine efflux yokhudzana ndi kutha, kuyambitsa CS-ndi-d-amphetamine-kumabweretsa kubwezeretsedwa kwa khalidwe lofunafuna mankhwala ndi makoswe. Behav Ubongo Res 120: 147-158.

  55. ↵
    1. Do Ribeiro Couto B,
    2. Aguilar MA,
    3. Rodríguez-Arias M,
    4. Miñarro J

    (2005) Kubwezeretsedwa kwa mtanda ndi cocaine ndi amphetamine ya malo opangidwa ndi morphine amakonda makoswe. Behav Pharmacol 16: 253-259.

  56. ↵
    1. Dunn JM,
    2. Kudzudzula BR,
    3. Licata SC,
    4. Pierce RC

    (2005) Kulamulira kobwerezabwereza kwa AMPA kapena metabotropic glutamate receptor agonist m'dera la makoswe amtunduwu amachititsa kuti khalidwe loipa la cocaine lichitike. Psychopharmacology (Berl) 179: 172-180.

  57. ↵
    1. Epstein DH,
    2. Preston KL,
    3. Stewart J,
    4. Shaham Y

    (2006) Potsatira chitsanzo chobwezeretsa mankhwala: kuwonetsetsa kuti ndondomeko yobwezeretsedweratu ikuvomerezeka. Psychopharmacology (Berl) 189: 1-16.

  58. ↵
    1. KR yotchuka,
    2. Kumaresan V,
    3. Sadri-Vakili G,
    4. Schmidt HD,
    5. Mierke DF,
    6. Cha JH,
    7. Pierce RC

    (2008) Kugulitsa kwa malonda a GluR2 AMPA receptors mumtundu wa accumcums umathandiza kwambiri kubwezeretsa kwa cocaine. J Neurosci 28: 11061-11070.

  59. ↵
    1. KR yotchuka,
    2. Schmidt HD,
    3. Pierce RC

    (2007) Pogwiritsidwa ntchito mkatikatikati mwa khungu kapena chipolopolo, wotsutsa wa NMDA AP-5 amabwezeretsanso khalidwe lakakina lofunafuna khoka. Neurosci Lett 420: 169-173.

  60. ↵
    1. Ferrario CR,
    2. Gorny G,
    3. Crombag HS,
    4. Li Y,
    5. Kolb B,
    6. Robinson TE

    (2005) Chiphalasitiki cha Neural ndi khalidweli chogwirizana ndi kusintha kwasintha kuchokera ku ntchito yogwiritsidwa ntchito ya cocaine. Biol Psychiatry 58: 751-759.

  61. ↵
    1. Ferrario CR,
    2. Li X,
    3. Wang X,
    4. Reimers JM,
    5. Uejima JL,
    6. Wolf ME

    (2010) Udindo wa kugawidwa kwa glutamate pamtengowu pofuna kulimbikitsanso kuti mankhwalawa asokonezeke. Neuropsychopharmacology 35: 818-833.

  62. ↵
    1. Fitzgerald LW,
    2. Ortiz J,
    3. Hamedani AG,
    4. Nestler EJ

    (1996) Mankhwala osokoneza bongo ndi kupanikizika kumawonjezera maonekedwe a magulu a GluR1 ndi NMDAR1 amtundu wothandizira pa kondomu: J Neurosci 16: 274-282.

  63. ↵
    1. Fletcher PJ,
    2. Robinson SR,
    3. Slippoy DL

    (2001) Kutanganidwa kale ndi (±) 3,4-methylenedioxy-methamphetamine (MDMA) imathandiza kuti munthu azipeza yekha mankhwala osokoneza bongo. Neuropsychopharmacology 25: 195-203.

  64. ↵
    1. Fuchs RA,
    2. Branham RK,
    3. Onani RE

    (2006) Kusiyana kwazitsulo zazing'ono zimaphatikizapo cocaine kufunafuna kudziletsa kapena kutha kwa maphunziro: chofunikira kwambiri pa dorsolateral caudate-putamen. J Neurosci 26: 3584-3588.

  65. ↵
    1. Fuchs RA,
    2. Eaddy JL,
    3. Su ZI,
    4. Bell GH

    (2007) Kuyanjana kwa amygdala odyetserako ziweto pamodzi ndi hippocampus osakanikirana ndi chigoba chotsutsana ndi mankhwala omwe amachititsa kuti mankhwalawa asokonezedwe. Eur J Neurosci 26: 487-498.

  66. ↵
    1. Fuchs RA,
    2. Evans KA,
    3. Ledford CC,
    4. Parker MP,
    5. Mlandu JM,
    6. Mehta RH,
    7. Onani RE

    (2005) Udindo wa dorsomedial prefrontal cortex, amygdala, ndi hippocampus osakanikirana ndi kubwezeretsedwa kwa cocaine kufunafuna makoswe. Neuropsychopharmacology 30: 296-309.

  67. ↵
    1. Fuchs RA,
    2. Evans KA,
    3. Parker MC,
    4. Onani RE

    (2004) Kuphatikizidwa kwakukulu kwa zigawo zapakati ndi zipolopolo za nucleus accumbens mu chikhalidwe chokhazikika chobwezeretsa cocaine kufunafuna makoswe. Psychopharmacology (Berl) 176: 459-465.

  68. ↵
    1. Fuchs RA,
    2. Onani RE

    (2002) Kusamalidwa kwapadera kwa abolinali kumathetseratu kusinthika-ndi kubwezeretsedwa kwa heroin kwa khalidwe lofuna kutentha kwa heroin mu makoswe. Psychopharmacology (Berl) 160: 425-433.

  69. ↵
    1. Ghasemzadeh MB,
    2. Permenter LK,
    3. Nyanja R,
    4. Worley PF,
    5. Kalivas PW

    (2003) Mapuloteni a Homer1 ndi mapulogalamu a AMPA amachititsa kuti mapuloteni a cocaine asokonezeke. Eur J Neurosci 18: 1645-1651.

  70. ↵
    1. Ghasemzadeh MB,
    2. Vasudevan P,
    3. Mueller C

    (2009a) Kukudziwitsidwa kwa malo otentha kwa cocaine kumagwirizanitsidwa ndi mtundu wosiyana wa malonda a glutamate receptor to postsnaptic density in prefrontal cortex: oyambirira ndi kuchepetsa kuchepetsa zotsatira. Pharmacol Biochem Behav 92: 383-392.

  71. ↵
    1. Ghasemzadeh MB,
    2. Windham LK,
    3. Nyanja RW,
    4. Acker CJ,
    5. Kalivas PW

    (2009b) Cocaine imayambitsa Homer1 yomweyo oyambirira jini kusindikizidwa mu mesocorticolimbic circuit: malamulo osagwirizana ndi dopamine ndi chizindikiro cha glutamate. Synapse 63: 42-53.

  72. ↵
    1. Giorgetti M,
    2. Hotsenpiller G,
    3. Ward P,
    4. Teppen T,
    5. Wolf ME

    (2001) Amphetamine-inachititsa mapulasitiki a AMPA receptors mu ventral tegmental m'dera: zotsatira pa extracellular magulu a dopamine ndi glutamate mu makoswe kusuntha makoswe. J Neurosci 21: 6362-6369.

  73. ↵
    1. Perekani S,
    2. London ED,
    3. Newlin DB,
    4. Villemagne VL,
    5. Liu X,
    6. Contoreggi C,
    7. Phillips RL,
    8. Kimes AS,
    9. Margolin A

    (1996) Kugwiritsa ntchito maulendo achikumbutso pa nthawi yachisangalalo cha cocaine. Proc Natl Acad Sci USA 93: 12040-12045.

  74. ↵
    1. Grignaschi G,
    2. Burbassi S,
    3. Zennaro E,
    4. Bendotti C,
    5. Cervo L

    (2004) Kokaine imodzi yokha imapangitsa kuti khalidwe likhale lolimbikitsa komanso limasintha mRNA yolemba GluR1 ndi GAP-43 mu makoswe. Eur J Neurosci 20: 2833-2837.

  75. ↵
    1. Hahn J,
    2. Chiyembekezo FW,
    3. Bonci A

    (2009) Matenda a cocaine osapitirira amachititsa kuti corticotropin-released-potential release of potential excitatory transmission mu ventral tegmental dopamine neurons. J Neurosci 29: 6535-6544.

  76. ↵
    1. Hamlin AS,
    2. Clemens KJ,
    3. Choi EA,
    4. McNally GP

    (2009) Phalaventricular thalamus amalumikizana mobwerezabwereza-kubwezera kubwezeretsa (kubwezeretsa) kwa kufunafuna mphotho kumaliziro. Eur J Neurosci 29: 802-812.

  77. ↵
    1. Henry DJ,
    2. Greene MA,
    3. White FJ

    (1989) Mafilimu a cocaine mu masoaccumbens dopamine system: mobwerezabwereza mautumiki. J Pharmacol Exp Ther 251: 833-839.

  78. ↵
    1. Henry DJ,
    2. White FJ

    (1991) Utsogoleri wa cocaine wochulukanso umapangitsa kuti D1 dopamine receptor udziwitsire mkati mwa khola la nucleus accumbens. J Pharmacol Exp Ther 258: 882-890.

  79. ↵
    1. Hooks MS,
    2. Duffy P,
    3. Striplin C,
    4. Kalivas PW

    (1994) Kulimbikitsana ndi kapangidwe kake kazakudya zotsatira za cocaine. Psychopharmacology (Berl) 115: 265-272.

  80. ↵
    1. Horger BA,
    2. Giles MK,
    3. Schenk S

    (1992) Kupuma kwa amphetamine ndi chikonga kumapangitsa makoswe kuti azidzipangira mankhwala ochepa a cocaine. Psychopharmacology (Berl) 107: 271-276.

  81. ↵
    1. Hotsenpiller G,
    2. Wolf ME

    (2002) Maselo a extracellular glutamate mu prefrontal cortex pamene akugwirizana ndi mayankho okhudzana ndi cocaine. Neuropharmacology 43: 1218-1229.

  82. ↵
    1. Huang CC,
    2. Lin HJ,
    3. Hsu KS

    (2007a) Utsogoleri wa cocaine wochulukitsidwa umathandizira kuti pakhale nthawi yambiri yomwe ingapangidwe mu makoswe. Cereb Cortex 17: 1877-1888.

  83. ↵
    1. Huang CC,
    2. Yang PC,
    3. Lin HJ,
    4. Hsu KS

    (2007b) Utsogoleri wa cocaine womwe umabwereza umapweteketsa gulu lachiŵiri la metabotropic glutamate yomwe imakhala ndi nthawi yaitali yokhala ndi vuto lachisokonezo m'matope omwe amagwiritsidwa ntchito popanga makina. J Neurosci 27: 2958-2968.

  84. ↵
    1. Itzhak Y,
    2. Martin JL

    (1999) Zotsatira za cocaine, chikonga, dizocipline ndi mowa pa makoswe ogulitsa ntchito: cocaine-mowa-sensitization umaphatikizapo kuperewera kwa dopamine operekera malonda. Kafukufuku wa Ubongo 818: 204-211.

  85. ↵
    1. Johnson DW,
    2. Glick SD

    (1993) Dopamine kumasulidwa ndi kagayidwe kamene kamene kamakhala mu nucleus accumbens ndi striatum ya makoswe ovomerezeka komanso osatsutsika a morphine. Pharmacol Biochem Behav 46: 341-347.

  86. ↵
    1. Joyce EM,
    2. Iversen SD

    (1979) Zotsatira za morphine zimagwiritsidwa ntchito m'madera amodzi ku mesencephalic dopamine maselo pamagalimoto omwe amangochitika pangodya. Neurosci Lett 14: 207-212.

  87. ↵
    1. Kalivas PW,
    2. Weber B

    (1988) Jekeseni wa Amphetamine mu mesralphalon ventral imalimbikitsa makoswe kuti apite kumbali yamphetamine ndi cocaine. J Pharmacol Exp Ther 245: 1095-1102.

  88. ↵
    1. Kalivas PW,
    2. Alesdatter JE

    (1993) Kuphatikizidwa kwa N-methyl-D-aspartate kukakamiza kulandirira mu ventral tegmental m'deralo ndi amygdala mu khalidwe kutsimikizira kuti cocaine. J Pharmacol Exp Ther 267: 486-495.

  89. ↵
    1. Kalivas PW,
    2. Duffy P

    (1990) Zotsatira za mankhwala osokoneza bongo komanso a cocaine tsiku lililonse pa extracellular dopamine mu nucleus accumbens. Synapse 5: 48-58.

  90. ↵
    1. Kalivas PW,
    2. Duffy P

    (1993) Nthawi ya extracellular dopamine ndi khalidweal kulimbikitsanso kuti cocaine. II. Dopamine perikarya. J Neurosci 13: 276-284.

  91. ↵
    1. Kalivas PW,
    2. Duffy P

    (1995) Ma receptors a D1 amawongolera kufalikira kwa glutamate m'dera la ventral tegmental. J Neurosci 15:5379–5388.

  92. ↵
    1. Kalivas PW,
    2. Duffy P

    (1998) Utsogoleri wa cocaine wochulukanso umasintha mtundu wa glutamate wochuluka m'dera la ventral tegmental. J Neurochem 70: 1497-1502.

  93. ↵
    1. Kalivas PW,
    2. McFarland K

    (2003) Kuzungulira maubongo ndi kubwezeretsedwa kwa khalidwe la cocaine. Psychopharmacology (Berl) 168: 44-56.

  94. ↵
    1. Kalivas PW,
    2. Stewart J

    (1991) Kupatsirana kwa Dopamine poyambitsa ndi kuwonetsa kwa mankhwala ndi kusokonezeka maganizo kwa magalimoto. Chikumbutso cha ubongo 16: 223-244.

  95. ↵
    1. Kantak KM,
    2. Black Y,
    3. Valencia E,
    4. Green-Jordan K,
    5. Eichenbaum HB

    (2002) Kusokonezeka kwa zotsatira za lidocaine popangitsa kuti amygdala azisamalidwe ndi zozizwitsa zisamayende bwino pakusungidwa ndi kubwezeretsedwa kwa khalidwe la cocaine mu makoswe. J Neurosci 22: 1126-1136.

  96. ↵
    1. Karreman M,
    2. Westerink BH,
    3. Moghaddam B

    (1996) Zosangalatsa za amino acid receptors mu ventral tegmental dera zimayendetsa dopamine kumasulidwa mu ventral striatum. J Neurochem 67: 601-607.

  97. ↵
    1. Katner SN,
    2. Weiss F

    (1999) Ethanol-yogwiritsidwa ntchito zowonongeka zimatsitsimutsa khalidwe lofuna kutentha kwa ethanol pambuyo poti zatha ndi kusintha mazira ochepa a dopamine mu nucleus accumbens. Mowa Wotulutsa Zakumwa za Mowa 23: 1751-1760.

  98. ↵
    1. Kau KS,
    2. Madayag A,
    3. Mantsch JR,
    4. Grier MD,
    5. Abdulhameed O,
    6. Baker DA

    (2008) Chotupitsa cha cystine-glutamate antiporter chikugwira ntchito mu nucleus accumbens imalimbikitsa kufunafuna mankhwala a cocaine. Neuroscience 155: 530-537.

  99. ↵
    1. Keiflin R,
    2. Kachilombo E,
    3. Cador M

    (2008) Kukhazikitsidwa kwa Cocaine mu makoswe: umboni wa ntchito yaikulu ya cocaine stimulus properties. Psychopharmacology (Berl) 197: 649-660.

  100. ↵
    1. CD Kilts,
    2. Schweitzer JB,
    3. Quinn CK,
    4. ZOKHUDZA RE,
    5. Faber TL,
    6. Muhammad F,
    7. Ely TD,
    8. Hoffman JM,
    9. Drexler KP

    (2001) Zochita za Neural zokhudzana ndi chilakolako cha mankhwala ozunguza bongo ku cocaine. Arch Gen Psychiatry 58: 334-341.

  101. ↵
    1. Kim JH,
    2. Austin JD,
    3. Tanabe L,
    4. Creekmore E,
    5. Vezina P

    (2005) Kugwiritsa ntchito mapulogalamu a magulu awiri a Gulu kumateteza mankhwala omwe amayamba chifukwa cha amphetamine. Eur J Neurosci 21: 295-300.

  102. ↵
    1. Kim JH,
    2. Vezina P

    (1998) Mavitamini a metabotropic glutamate ndi ofunikira kuti azitonthozedwa ndi amphetamine. Neuroreport 9: 403-406.

  103. ↵
    1. Kita H,
    2. Kitai ST

    (1990) Amygdaloid malingaliro a kanyumba ka kutsogolo ndi striatum mu khola. J Comp Neurol 298: 40-49.

  104. ↵
    1. Knackstedt LA,
    2. Kalivas PW

    (2007) Kuonjezeredwa kwa cocaine kudziyang'anira bwino kumapangitsa kubwezeretsedwa kwa mankhwala osamalidwa koma kusalimbikitsa khalidwe. J Pharmacol Exp Ther 322: 1103-1109.

  105. ↵
    1. Knackstedt LA,
    2. LaRowe S,
    3. Mardikian P,
    4. Malcolm R,
    5. Upadhyaya H,
    6. Odala S,
    7. Markou A,
    8. Kalivas PW

    (2009) Udindo wa kansitini-glutamate kusinthanitsa ndi chikonga kudalira makoswe ndi anthu. Biol Psychiatry 65: 841-845.

  106. ↵
    1. Knackstedt LA,
    2. Melendez RI,
    3. Kalivas PW

    (2010) Ceftriaxone imabwezeretsanso malo otchedwa glutamate homeostasis ndipo imalepheretsa kubwerera ku cocaine kufunafuna. Biol Psychiatry 67: 81-84.

  107. ↵
    1. Koob GF,
    2. Volkow ND

    (2010) Mankhwala osokoneza bongo. Neuropsychopharmacology 35: 217-238.

  108. ↵
    1. Kourrich S,
    2. Rothwell PE,
    3. Klug JR,
    4. Thomas MJ

    (2007) Chidziwitso cha Cocaine chimagwira ntchito yokhala ndi mapuloteni ochepa kwambiri omwe amakhalapo pamtunduwu. J Neurosci 27: 7921-7928.

  109. ↵
    1. Kruzich PJ,
    2. Onani RE

    (2001) Zopereka zosiyana siyana za amygdala omwe ali kumbali ndi pakati pa kupeza ndi kufotokoza kwa chizoloŵezi chobwezeretsa ku cocaine. J Neurosci 21: RC155.

  110. ↵
    1. LaLumiere RT,
    2. Kalivas PW

    (2008) Glutamate kumasulidwa mu nucleus accumbens msingi ndifunikira kwa heroin kufunafuna. J Neurosci 28: 3170-3177.

  111. ↵
    1. Ledford CC,
    2. Fuchs RA,
    3. Onani RE

    (2003) Kuyambanso kubwezeretsedwa kwa khalidwe la cocaine kutsata pambuyo D-amphetamine kulowetsedwa mu amolgalaal amygdala. Neuropsychopharmacology 28: 1721-1729.

  112. ↵
    1. Leith NJ,
    2. Kuczenski R

    (1982) Ziwalo ziwiri zosagwirizana ndi khalidwe lachidziwitso cha makhalidwe omwe amatsatira mobwerezabwereza amphetamine. Psychopharmacology (Berl) 76: 310-315.

  113. ↵
    1. Lenoir M,
    2. Ahmed SH

    (2007) Kubwezeretsedwanso kotsutsana ndi abambo kumaphatikizapo kugwiritsira ntchito heroin ntchito ndi dissociable kuchokera ku heroin mphotho ndi kulimbikitsa. Neuropsychopharmacology 32: 616-624.

  114. ↵
    1. Lett BT

    (1989) Kuwonetsedwa kobwerezabwereza kumawonjezereka osati kuchepetsa zotsatira zabwino za amphetamine, morphine, ndi cocaine. Psychopharmacology (Berl) 98: 357-362.

  115. ↵
    1. Li SM,
    2. Ren YH,
    3. Zheng JW

    (2002) Zotsatira za 7-nitroindazole pobwezeretsa mankhwala osokoneza bongo a D-methamphetamine-omwe amachititsa kuti azikonda malo. Eur J Pharmacol 443: 205-206.

  116. ↵
    1. Li Y,
    2. Hu XT,
    3. Berney TG,
    4. Vartanian AJ,
    5. CD yolimba,
    6. Wolf ME,
    7. White FJ

    (1999) Onse omwe amatsutsana ndi glutamate ndi operesal cortex zilonda zimapewa kukopa kwa cocaine kulimbikitsa komanso kugwiritsira ntchito mankhwala. Synapse 34: 169-180.

  117. ↵
    1. Lodge DJ,
    2. Chisomo AA

    (2008) Amphetamine kuyendetsa galimoto ya hippocampal ya mesolimbic dopamine neurons: njira yothandizira khalidwe. J Neurosci 28: 7876-7882.

  118. ↵
    1. Lu W,
    2. Monteggia LM,
    3. Wolf ME

    (2002) Katundu wambiri wa amphetamine kapena cocaine sichimasintha mawu a AMPA omwe amalandira chiwonetsero m'magulu. Neuropsychopharmacology 26: 1-13.

  119. ↵
    1. Madayag A,
    2. Kau KS,
    3. Lobner D,
    4. Mantsch JR,
    5. Wisniewski S,
    6. Baker DA

    (2010) Kupanga mankhwala osokoneza bongo kumathandiza kuti munthu ayambe kubwezeretsa vutoli: kusintha kwa mazira ndi kusintha kwadzidzidzi kwa makoswe. J Neurosci 30: 210-217.

  120. ↵
    1. Madayag A,
    2. Lobner D,
    3. Kau KS,
    4. Mantsch JR,
    5. Abdulhameed O,
    6. Kumva M,
    7. Grier MD,
    8. Baker DA

    (2007) Kachitidwe kabwino ka N-acetylcysteine ​​kamapangitsa kuti mankhwala a cocaine azidalira mapulasitiki. J Neurosci 27: 13968-13976.

  121. ↵
    1. Mameli M,
    2. Balland B,
    3. Luján R,
    4. Lüscher C

    (2007) Mwamsanga kaphatikizidwe ndi kusinthasintha kwa GluR2 kwa mGluR-LTD kudera la ventral tegmental. Science 317: 530-533.

  122. ↵
    1. Mameli M,
    2. Halbout B,
    3. Creton C,
    4. Engblom D,
    5. Parkitna JR,
    6. Spanagel R,
    7. Lüscher C

    (2009) Mapuloteni otchedwa coaptic plasticine: Kulimbikira mu VTA kumayambitsa kusintha kwa NAC. Nat Neurosci 12: 1036-1041.

  123. ↵
    1. Mardikian PN,
    2. LaRowe SD,
    3. Odala S,
    4. Kalivas PW,
    5. Malcolm RJ

    (2007) Mayesero otseguka a N-acetylcysteine ​​pochiza matenda a cocaine: kuphunzira kwa woyendetsa ndege. Prog Neuropsychopharmacol Nthenda ya Psychiatry 31: 389-394.

  124. ↵
    1. Marinelli M,
    2. Le Moal M,
    3. Piazza PV

    (1998) Kuchepetsa mphamvu za magulu a heroin koma osati a kappa agonist RU 51599. Psychopharmacology (Berl) 139: 281-285.

  125. ↵
    1. Mattson BJ,
    2. Koya E,
    3. Simmons DE,
    4. Mitchell TB,
    5. Berkow A,
    6. Crombag HS,
    7. Hope BT

    (2008) Chidziwitso chodziwika bwino cha ntchito yopangira mankhwala a cocaine ndi zochitika za neuronal zomwe zimagwirizanitsidwa ndi makoswe. Eur J Neurosci 27: 202-212.

  126. ↵
    1. McFarland K,
    2. Davidge SB,
    3. Lapish CC,
    4. Kalivas PW

    (2004) Limbic ndi motor circry zomwe zapangitsa kuti abwezeretsenso khansa ya cocaine. J Neurosci 24: 1551-1560.

  127. ↵
    1. McFarland K,
    2. Kalivas PW

    (2001) Bungwe lozungulira lomwe limayambitsa matenda a cocaine limayambiranso. J Neurosci 21: 8655-8663.

  128. ↵
    1. McFarland K,
    2. Lapish CC,
    3. Kalivas PW

    (2003) Kutulutsira patsogolo kwa glutamate m'chigawo chapakati cha nyukiliya kumabweza pakati pobwezeretsa mankhwala osokoneza bongo a cocaine. J Neurosci 23: 3531-3537.

  129. ↵
    1. McLaughlin J,
    2. Onani RE

    (2003) Kusankha kwapangidwe ka dorsomedial prefrontal cortex ndi basolateral amygdala attenuates okhazikika-cued kubwezeretsanso kozimitsa kochita kufuna cocaine mu makoswe. Psychopharmacology (Berl) 168: 57-65.

  130. ↵
    1. Meil WM,
    2. Onani RE

    (1996) Yododometsa poyambiranso kuyankha pambuyo pochoka kwa nthawi yayitali kuchokera ku kudzipereka kwa cocaine m'miyani: mtundu wachinyama wobwereranso. Behav Pharmacol 7: 754-763.

  131. ↵
    1. Meil WM,
    2. Onani RE

    (1997) Zilonda za basolateral amygdala zimathetsa mphamvu zomwe zimagwiritsidwa ntchito ndi mankhwala kuti zibwezeretsenso poyankha pakubwera kwa cocaine wokha. Behav Ubongo Res 87: 139-148.

  132. ↵
    1. Mendrek A,
    2. Blaha CD,
    3. Phillips AG

    (1998) Kuwonetsa makoswe kusanachitike amphetamine kumapangitsa kudzilamulira kwa mankhwalawa moyenera. Psychopharmacology (Berl) 135: 416-422.

  133. ↵
    1. Mickiewicz AL,
    2. Dallimore JE,
    3. Napier TC

    (2009) Pralid pallidum imathandizira kwambiri pakukweza ndikuwonetsa chidwi cha morphine. Neuropsychopharmacology 34: 874-886.

  134. ↵
    1. Moga MM,
    2. Weis RP,
    3. Moore RY

    (1995) Makina olimbikira a phulaic phulaic mu rat. J Comp Neurol 359: 221-238.

  135. ↵
    1. Moran MM,
    2. McFarland K,
    3. Melendez RI,
    4. Kalivas PW,
    5. Asodzi a JK

    (2005) cystine / glutamate kusinthana kumayendetsa metabotropic glutamate receptor presynaptic kuletsa kosangalatsa kwa kufalikira ndi chiopsezo pakufunafuna cocaine. J Neurosci 25: 6389-6393.

  136. ↵
    1. Morgan D,
    2. Liu Y,
    3. Roberts DC

    (2006) Chidwi cholimba komanso chopitilira mu mphamvu za cocaine. Neuropsychopharmacology 31: 121-128.

  137. ↵
    1. Morgan D,
    2. Roberts DC

    (2004) Kupereka mphamvu zolimbitsa thupi za cocaine wotsatira kudziletsa pakokha. Neurosci Biobehav Rev 27: 803-812.

  138. ↵
    1. Moro H,
    2. Sato H,
    3. Ida I,
    4. Oshima A,
    5. Sakurai N,
    6. Shihara N,
    7. Horikawa Y,
    8. Mikuni M

    (2007) Zotsatira za SKF-38393, dopamine D1 receptor agonist pofotokozera za amphetamine-anachititsa chidwi chokhudza mtima komanso kufotokoza kwa geni arc koyambirira kwamphongo. Pharmacol Biochem Behav 87: 56-64.

  139. ↵
    1. Moussawi K,
    2. Pacchioni A,
    3. Moran M,
    4. Olive MF,
    5. Gass JT,
    6. Lavin A,
    7. Kalivas PW

    (2009) N-Acetylcysteine ​​imabwezeretsa metaplasticity ya cocaine. Nat Neurosci 12: 182-189.

  140. ↵
    1. Mueller D,
    2. Stewart J

    (2000) Kokonzedwa ndi Cocaine wokhala ndi malo oyikirako: kubwezeretsedwanso mwa kupukusa jakisoni wa cocaine atatha. Behav Ubongo Res 115: 39-47.

  141. ↵
    1. Neisewander JL,
    2. Baker DA,
    3. Fuchs RA,
    4. Tran-Nguyen LT,
    5. Palmer A,
    6. Marshall JF

    (2000) Kufotokozera kwa mapuloteni a Fos ndi mikhalidwe yofunafuna cocaine mu makoswe atatha kukhala panjira yodziyimira pawokha ya cocaine. J Neurosci 20: 798-805.

  142. ↵
    1. Neisewander JL,
    2. O'Dell LE,
    3. Tran-Nguyen LT,
    4. Castañeda E,
    5. Fuchs RA

    (1996) Dopamine imasefukira mu nambala ya msurayi pakutha ndikuyambiranso kwamakhalidwe oyendetsa pakompyuta. Neuropsychopharmacology 15: 506-514.

  143. ↵
    1. Nelson CL,
    2. Milovanovic M,
    3. Wetter JB,
    4. Ford KA,
    5. Wolf ME

    (2009) Kulimbikitsa kukhudzika kwa amphetamine sikumayendera limodzi ndi kusintha kwa glutamate receptor surface expression mu rat nucleus accumbens. J Neurochem 109: 35-51.

  144. ↵
    1. Nelson CL,
    2. Wetter JB,
    3. Milovanovic M,
    4. Wolf ME

    (2007) The laterodorsal tegmentum imathandizira chidwi cha amphetamine. Neuroscience 146: 41-49.

  145. ↵
    1. Nisell M,
    2. Nomikos GG,
    3. Hertel P,
    4. Panagis G,
    5. Svensson TH

    (1996) Mkhalidwe wodziyimira pawokha wa kusunthika kwa phenomotor ndi masocortical dopamine kumasulidwa kutsatira chithandizo cha chikonga cha muyezo. Synapse 22: 369-381.

  146. ↵
    1. O'Brien CP

    (1997) Ma pharmacotherapies ofotokoza mafunso osiyanasiyana osokoneza bongo. Science 278: 66-70.

  147. ↵
    1. OConnor WT

    (2001) Nuroanatomy yogwira ya njira yodutsa ya stralopriidal GABA. Malo atsopano ochitira mankhwalawa. J Neurosci Njira 109: 31-39.

  148. ↵
    1. Oades RD,
    2. Halliday GM

    (1987) Mchitidwe wa Ventral tegmental (A10): matenda a neurobiology. 1. Anatomy ndi kugwirizana. Resin ya ubongo 434: 117-165.

  149. ↵
    1. Omelchenko N,
    2. Sesack SR

    (2005) Magawo osinthika a laterodorsal kuti azindikiritse kuchuluka kwa maselo m'dera la rat ventral gawo. J Comp Neurol 483: 217-235.

  150. ↵
    1. Omelchenko N,
    2. Sesack SR

    (2007) Zowonjezera za Glutamate synaptic to neurral gawo lama neuron mu gawo zimachokera makamaka ku magawo am'munsi. Neuroscience 146: 1259-1274.

  151. ↵
    1. Park WK,
    2. Bari AA,
    3. Jey AR,
    4. Anderson SM,
    5. Spealman RD,
    6. Rowlett JK,
    7. Pierce RC

    (2002) Cocaine yoyendetsedwa mu medial prefrontal cortex imabwezeretsa chikhalidwe chofunafuna cocaine mwakuwonjezera kufalitsa kwa AMPA receptor-mediated glutamate kufalitsa kwa ma nucleus accumbens. J Neurosci 22: 2916-2925.

  152. ↵
    1. Parker LA,
    2. Mcdonald RV

    (2000) Kubwezeretsanso zonse zomwe zimakonda malo okonzedwa komanso malo okonzedwa ndi malo osokoneza bongo. Pharmacol Biochem Behav 66: 559-561.

  153. ↵
    1. Parsons LH,
    2. Justice JB Jr.

    (1993) Serotonin ndi sensopization ya dopamine mu ma nyukiliya amasonkhanitsa, dera lozungulira gawo, ndi dorsal raphe nucleus kutsatira kubwereza kokhazikika kwa cocaine. J Neurochem 61: 1611-1619.

  154. ↵
    1. Paulson PE,
    2. Camp DM,
    3. Robinson TE

    (1991) Nthawi yochepetsetsa kwakanthawi kakhalidwe komanso kulimbikira kwamakhalidwe pokhudzana ndi kuzungulira kwa ubongo wa monoamine panthawi yakubwezeretsedwa kwa amphetamine mu makoswe. Psychopharmacology (Berl) 103: 480-492.

  155. ↵
    1. Peleg-Raibstein D,
    2. Feldon J

    (2008) Zotsatira zakuchoka kwa kuchuluka kwa amphetamine pazowopsa zamkati ndi mayankho a dopamine mu medial prefrontal cortex. Behav Ubongo Res 186: 12-22.

  156. ↵
    1. Peters J,
    2. Kalivas PW

    (2006) Gulu lachiwiri la metabotropic glutamate receptor agonist, LY379268, limalepheretsa khalidwe la cocaine- komanso lofunafuna chakudya m'miyamba. Psychopharmacology 186: 143-149.

  157. ↵
    1. Peters J,
    2. LaLumiere RT,
    3. Kalivas PW

    (2008) Infralimbic prefrontal cortex imayang'anira zoletsa ofuna cocaine kuzimitsa makoswe. J Neurosci 28: 6046-6053.

  158. ↵
    1. Peterson JD,
    2. Wolf ME,
    3. White FJ

    (2000) Kusintha kwa kusintha kwa ma medial prefrontal cortex neurons kuti glutamate ndi dopamine atachotsedwa pamankhwala obwereza amphetamine. Synapse 36: 342-344.

  159. ↵
    1. Phillips AG,
    2. Di Ciano P

    (1996) Kusintha kwakhalidwe kumayambitsa kudzipanga kwamphamvu kwa cocaine ndi makoswe. Psychopharmacology (Berl) 124: 279-281.

  160. ↵
    1. Piazza PV,
    2. Deminiere JM,
    3. Le Moal M,
    4. Simon H

    (1990) Kupsinjika- komanso kuphatikizira kwa zamankhwala kumawonjezera chiopsezo pakupeza kudzisamalira. Resin ya ubongo 514: 22-26.

  161. ↵
    1. Pierce RC,
    2. Bell K,
    3. Duffy P,
    4. Kalivas PW

    (1996a) Mobwerezabwereza cocaine augments wosangalatsa wa amino acid kufalitsa mu nyukiliya amasonkhana kokha mu makoswe atakhala ndi chidwi champhamvu. J Neurosci 16: 1550-1560.

  162. ↵
    1. Pierce RC,
    2. Wobadwa B,
    3. Adams M,
    4. Kalivas PW

    (1996b) Kukonzanso kwina kwa mkati mwa mkati mwa SKF-38393 kumapangitsa chidwi ndi zamitsempha pamavuto azotsatira za cocaine. J Pharmacol Exp Ther 278: 384-392.

  163. ↵
    1. Pierce RC,
    2. Kalivas PW

    (1997a) Chithunzithunzi cha mawonekedwe a kuchitira chidwi kwamphamvu kwa amphetamine monga psychostimulants. Chikumbutso cha ubongo 25: 192-216.

  164. ↵
    1. Pierce RC,
    2. Kalivas PW

    (1997b) Cocaine wobwereza umasintha momwe amphetamine amatulutsira dopamine. J Neurosci 17: 3254-3261.

  165. ↵
    1. Pierce RC,
    2. Reeder DC,
    3. Hick J,
    4. Morgan ZR,
    5. Kalivas PW

    (1998) zotupa za Ibotenic acid za dorsal prefrontal cortex zimasokoneza kufotokoza kwa chidwi cha cocaine. Neuroscience 82: 1103-1114.

  166. ↵
    1. Ping A,
    2. Xi J,
    3. Prasad BM,
    4. Wang MH,
    5. Kruzich PJ

    (2008) Zophatikiza za nyukiliya zimapeza chimbudzi ndi chipolopolo GluR1 yokhala ndi ma AMPA receptors ku AMPA- ndi cocaine-primed kubwezeretsanso kwa cocaine wofunafuna. Resin ya ubongo 1215: 173-182.

  167. ↵
    1. Post RM,
    2. Contel NR

    (1983) Maphunziro aumunthu ndi nyama a cocaine: tanthauzo la kufalikira kwamakhalidwe, mu Stimulants: Neurochemical, Behavioral, and Clinical Perspectives (Creese I ed) pp 169-203, Raven Press, New York.

  168. ↵
    1. Post RM,
    2. Weiss SR,
    3. Pert A

    (1992) Kuchulukitsa komanso kuyambitsa mavuto obwera chifukwa cha kayendedwe ka cocaine, mu Cocaine: Pharmacology, Physiology and Clinical Strategies (Lakoski JM, Galloway MP, White FJ eds) pp 115-161, CRC Press, Ann Arbor, MI.

  169. ↵
    1. Ranaldi R,
    2. Pocock D,
    3. Zereik R,
    4. RA wanzeru

    (1999) Kusinthasintha kwa ma dopamine mu nyukiliya kumazungulira pakukonza, kutha, ndikukhazikitsanso kuyendetsa kwamkati kwa D-amphetamine. J Neurosci 19: 4102-4109.

  170. ↵
    1. Reid MS,
    2. Berger SP

    (1996) Umboni wotsitsa chidwi cha minofu yokhala ndi cocaine yomwe imapangitsa kuti amasulidwe amasulidwe a glutamate. Neuroreport 7: 1325-1329.

  171. ↵
    1. Robinson TE,
    2. Becker JB

    (1986) Kupirira kusintha mu ubongo ndi khalidwe lopangidwa ndi maulamuliro a amphetamine osatha: kafukufuku ndi kuyesa zitsanzo zamtundu wa amphetamine psychosis. Resin ya ubongo 396: 157-198.

  172. ↵
    1. Robinson TE,
    2. Berridge KC

    (2003) Zowonjezera. Annu Rev Psychol 54: 25-53.

  173. ↵
    1. Robinson TE,
    2. Berridge KC

    (2008) Ndemanga. Chikhumbo chofuna kukopa zolimbikitsa izi: mavuto ena apano. Philos Trans R Soc Lond B Biol Sci 363: 3137-3146.

  174. ↵
    1. Robinson TE,
    2. Jurson PA,
    3. Bennett JA,
    4. Bentgen KM

    (1988) Kulimbikitsidwa kosalekeza kwa dopamine neurotransication mu ventral striatum (nucleus accumbens) yopangidwa ndi zokumana nazo zam'mbuyomu ndi (+) - amphetamine: kafukufuku wama microbialysis pamiyendo yosuntha. Resin ya ubongo 462: 211-222.

  175. ↵
    1. Roger JL,
    2. Ghee S,
    3. Onani RE

    (2008) Maseweredwe abwinobwino omwe abwezeretsanso mikhalidwe yofunafuna heroin pamtundu wa nyama yobwereranso. Neuroscience 151: 579-588.

  176. ↵
    1. Saal D,
    2. Dong Y,
    3. Bonci A,
    4. Malenka RC

    (2003) Kugwiritsa ntchito mankhwala osokoneza bongo komanso kupsinjika kumayambitsa chizolowezi chofanana cha synaptic mu dopamine neurons. Neuron 37: 577-582.

  177. ↵
    1. Samson HH,
    2. Chappell A,
    3. Slawecki C,
    4. Hodge C

    (1999) Zotsatira za microinjection ya d-amphetamine mu n. Kuchepetsa kumapeto kwa gawo lakumapeto kwa Mowa. Pharmacol Biochem Behav 63: 159-165.

  178. ↵
    1. Sanchez CJ,
    2. Bailie TM,
    3. Wu WR,
    4. Li N,
    5. Sorg BA

    (2003) Kugwiritsa kwa dopamine d1-ngati receptor activation mu rat medial prefrontal cortex alters stress- ndi cocaine-yomwe yalimbikitsa kubwezeretsa komwe akukonda. Neuroscience 119: 497-505.

  179. ↵
    1. Sari Y,
    2. Smith KD,
    3. Ali PK,
    4. Rebec GV

    (2009) Kubwezeretsanso kwa GLT1 kumathandizira kubwezeretsanso kochita kufuna kwa cocaine m'makhola. J Neurosci 29: 9239-9243.

  180. ↵
    1. Schilström B,
    2. Yaka R,
    3. Argilli E,
    4. Suvarna N,
    5. Schumann J,
    6. Chen BT,
    7. Karman M,
    8. Singh V,
    9. Mailliard WS,
    10. Ron D,
    11. Et al

    . (2006) Cocaine imathandizira ma NMDA receptor-mediated currents mumagawo a ventral tegmental area kudzera dopamine D5 receptor-based receptorution of NMDA receptors. J Neurosci 26: 8549-8558.

  181. ↵
    1. Schmidt HD,
    2. Anderson SM,
    3. Pierce RC

    (2006) Kukondoweza kwa D1-kapena D2 dopamine receptors mu chipolopolo, koma osati pachimake, cha nucleus accumbens imabwezeretsanso khalidwe lomwe limafuna cocaine mu rat. Eur J Neurosci 23: 219-228.

  182. ↵
    1. Schmidt HD,
    2. KR yotchuka,
    3. Pierce RC

    (2009) Ma membala a cocaine omwe amapezeka ndi cocaine amafunafuna PPTg / LDT. Eur J Neurosci 30: 1358-1369.

  183. ↵
    1. Schumann J,
    2. Matzner H,
    3. Michaeli A,
    4. Yaka R

    (2009) NR2A / B-wokhala ndi NMDA receptors amalumikizira cocaine-induction synaptic plasticity mu VTA ndi cocaine psychomotor sensitization. Neurosci Lett 461: 159-162.

  184. ↵
    1. Schumann J,
    2. Yaka R

    (2009) Kuchotsedwa kwachikonzero kwakanthawi kokhazikika komwe kumawonetsa cocaine mobwerezabwereza kumawonjezera NMDA receptor expression ndi ntchito ya ERK mu nucleus ascub. J Neurosci 29: 6955-6963.

  185. ↵
    1. Onani RE

    (2009) Dopamine D1 receptor antagonism mu prelimbic cortex imalepheretsa kubwezeretsanso kwa heroin-mu mtundu wachinyama kubwerera. Int J Neuropsychopharmacol 12: 431-436.

  186. ↵
    1. Onani RE,
    2. Kruzich PJ,
    3. Grimm JW

    (2001) Dopamine, koma osati kususuka, receptor blockade in the basolateral amygdala attenuates champhumphu mu mtundu wa rat womwe ungayambirenso kusuta fodya. Psychopharmacology (Berl) 154: 301-310.

  187. ↵
    1. Sepehrizadeh Z,
    2. Bahrololoumi Shapourabadi M,
    3. Ahmadi S,
    4. Hashemi Bozchlou S,
    5. Zarrindast MR,
    6. Sahebgharani M

    (2008) Inachepetsa AMPA GluR2, koma osati GluR3, mawu a mRNA mu rat amygdala ndi dorsal hippocampus kutsatira morphine-inachititsa chidwi mphamvu. Clin Exp Pharmacol Physiol 35: 1321-1330.

  188. ↵
    1. Shaham Y,
    2. Erb S,
    3. Stewart J

    (2000a) Kuyambiranso kupsinjika kwa heroin ndi cocaine wofunafuna makoswe: kuwunika. Chikumbutso cha ubongo 33: 13-33.

  189. ↵
    1. Shaham Y,
    2. Highfield D,
    3. Delfs J,
    4. Leung S,
    5. Stewart J

    (2000b) Clonidine imalepheretsa kubwezeretsanso kwa heroin kufunafuna makoswe: zotsatira zomwe sizimayima kwa locus coeruleus noradrenergic neurons. Eur J Neurosci 12: 292-302.

  190. ↵
    1. Shaham Y,
    2. Stewart J

    (1995) Kupsinjika kumabwezeretsa-kufunafuna kwa heroin mu nyama zopanda mankhwala: zotsatira zomwe zimayeseza heroin, osabweza. Psychopharmacology (Berl) 119: 334-341.

  191. ↵
    1. Shalev U,
    2. Grimm JW,
    3. Shaham Y

    (2002) Neurobiology yobwereranso ku heroin ndi cocaine kufunafuna: kuwunika. Pharmacol Rev 54: 1-42.

  192. ↵
    1. Shinonaga Y,
    2. Takada M,
    3. Mizuno N

    (1994) Topographic bungwe la zolingalira kuchokera ku basolateral amygdaloid nucleus to the prefrontal cortex and nucleus accumbens in the rat. Neuroscience 58: 389-397.

  193. ↵
    1. Shippenberg TS,
    2. LeFevour A,
    3. Mchimake C

    (1996) κ-Opioid receptor agonists amaletsa chidwi cha zotsatira zabwino za cocaine. J Pharmacol Exp Ther 276: 545-554.

  194. ↵
    1. Shoaib M,
    2. Benwell ME,
    3. Akbar MT,
    4. Stolerman IP,
    5. Balfour DJ

    (1994) Kusintha kwa machitidwe ndi ma neurochemical ku nikotini m'makola: kukopa kwa otsutsa a NMDA. Br J Pharmacol 111: 1073-1080.

  195. ↵
    1. Sorg BA,
    2. Davidson DL,
    3. Kalivas PW,
    4. Prasad BM

    (1997) Mobwerezabwereza tsiku ndi tsiku osinthitsa mankhwala osokoneza bongo a cocaine omwe amapangitsa kuti chiwonjezere cha extracellular dopamine mu cortex yamankhwala. J Pharmacol Exp Ther 281: 54-61.

  196. ↵
    1. Sorg BA,
    2. Li N,
    3. Wu WR

    (2001) Dopamine D1 receptor activation mu medial prefrontal cortex imalepheretsa kufotokoza kwa sensitization ya cocaine. J Pharmacol Exp Ther 297: 501-508.

  197. ↵
    1. Steketee JD

    (1998) Injection ya SCH 23390 kulowa mu gawo lothana ndi ventral imalepheretsa kukula kwa mitsempha koma osati yokhudza chidwi ndi cocaine. Behav Pharmacol 9: 69-76.

  198. ↵
    1. Steketee JD,
    2. Walsh TJ

    (2005) Kubayidwa mobwerezabwereza kwa sodium yonkitsa mu medial prefrontal cortex kumapangitsa chidwi cha cocaine m'miyamba. Psychopharmacology (Berl) 179: 753-760.

  199. ↵
    1. Stephans SE,
    2. Yamamoto NDI

    (1995) Kukhudzidwa mobwerezabwereza kwa methamphetamine pa dopamine ndi glutamate efflux mu rat prefrontal cortex. Resin ya ubongo 700: 99-106.

  200. ↵
    1. Stewart J

    (1984) Kukonzanso machitidwe a heroin ndi cocaine wodziyang'anira mu makondomu mwa kugwiritsa ntchito morphine mwa malo osokoneza bongo. Pharmacol Biochem Behav 20: 917-923.

  201. ↵
    1. Stewart J,
    2. Vezina P

    (1989) Microinjections ya Sch-23390 kulowa mu gawo lachigawo chodutsa ndi substantia nigra par reticulata ikuwonetsa kukula kwa chidwi ndi zotsatira zoyambitsa zochita za amphetamine. Resin ya ubongo 495: 401-406.

  202. ↵
    1. Dzuwa W,
    2. Akins CK,
    3. Zosangalatsa AE,
    4. Rebec GV

    (2005) ma Ionotropic glutamate receptors omwe ali m'dera lachigawo lachigawo amawongolera mikhalidwe yofunafuna cocaine m'makhola. Neuropsychopharmacology 30: 2073-2081.

  203. ↵
    1. Dzuwa W,
    2. Rebec GV

    (2003) Lidocaine inactivation ya ventral subiculum imatsata chikhalidwe chofuna cocaine m'makhola. J Neurosci 23: 10258-10264.

  204. ↵
    1. Dzuwa W,
    2. Rebec GV

    (2005) Udindo wa preortalal cortex D1-ngati D2-ngati receptors mu kakhalidwe kosaka cocaine mu makoswe. Psychopharmacology (Berl) 177: 315-323.

  205. ↵
    1. Suto N,
    2. Austin JD,
    3. Tanabe LM,
    4. Kramer MK,
    5. Wright DA,
    6. Vezina P

    (2002) Kuwonetsedwa koyambirira kwa VTA amphetamine kumathandizira kudziphatika kwa cocaine pansi pa ndandanda yowongolera pang'onopang'ono modalira D1 dopamine receptor. Neuropsychopharmacology 27: 970-979.

  206. ↵
    1. Suto N,
    2. Tanabe LM,
    3. Austin JD,
    4. Creekmore E,
    5. Pham CT,
    6. Vezina P

    (2004) Kudziwitsidwa kwam'mbuyo kwa psychostimulants kumathandizira kubwezeretsedwanso kwa cocaine wofunsidwa ndi nucleus accumbens AMPA. Neuropsychopharmacology 29: 2149-2159.

  207. ↵
    1. Takada M,
    2. Campbell KJ,
    3. Moriizumi T,
    4. Hattori T

    (1990) Pa chiyambi cha dopaminergic innervation ya paraventricular thalamic nucleus. Neurosci Lett 115: 33-36.

  208. ↵
    1. Tanabe LM,
    2. Suto N,
    3. Creekmore E,
    4. Steinmiller CL,
    5. Vezina P

    (2004) blockade ya D2 dopamine receptors mu VTA imathandizira kupititsa patsogolo kwotalikirapo kwa locomotor activating of amphetamine. Behav Pharmacol 15: 387-395.

  209. ↵
    1. Tecuapetla F,
    2. Patel JC,
    3. Xenias H,
    4. Chingerezi D,
    5. Tadros I,
    6. Shah F,
    7. Berlin J,
    8. Deisseroth K,
    9. Rice INE,
    10. Tepper JM,
    11. Et al

    . (2010) Zizindikiro za Glutamatergic zolemba ndi mesolimbic dopamine neurons mu ma nucleus accumbens. J Neurosci 30: 7105-7110.

  210. ↵
    1. Thomas MJ,
    2. Bakuman C,
    3. Bonci A,
    4. Malenka RC

    (2001) Kupsinjika kwanthawi yayitali mu nyukiliya imasonkhanitsa: chosakanikirana cha neural cha sensitization ya cocaine. Nat Neurosci 4: 1217-1223.

  211. ↵
    1. Thomas MJ,
    2. Kalivas PW,
    3. Shaham Y

    (2008) Kutsegula m'mimba mu disolimbic dopamine dongosolo ndi mowa wa cocaine. Br J Pharmacol 154: 327-342.

  212. ↵
    1. Torregrossa MM,
    2. Tang XC,
    3. Kalivas PW

    (2008) Kutsatsa kwa glutamatergic kuchokera ku preortal cortex kupita ku nucleus accumbens koyambirira kumafunikira kuti cocaine woyambitsa amachepetsa mu gawo la porral pallidal GABA. Neurosci Lett 438: 142-145.

  213. ↵
    1. Tran-Nguyen LT,
    2. Fuchs RA,
    3. Coffy GP,
    4. Baker DA,
    5. O'Dell LE,
    6. Neisewander JL

    (1998) Kusintha kokhazikika kwa mikhalidwe yofunafuna cocaine komanso kuchuluka kwa dopamine ya extracellular mu amygdala panthawi yochotsa cocaine. Neuropsychopharmacology 19: 48-59.

  214. ↵
    1. Tzschentke TM,
    2. Schmidt WJ

    (1998) Zodzikongoletsa za quinolinic acid zotupa za rat prelimbic medial prefrontal cortex zimakhudza cocaine- ndi MK-801-, koma osati morphine- komanso mphotho ya amphetamine komanso kuyambitsa ma psychomotor monga momwe amakondera ndi malo okonda paradigm. Behav Ubongo Res 97: 115-127.

  215. ↵
    1. Tzschentke TM,
    2. Schmidt WJ

    (2000) Kusiyana kwakanthawi kwa zotupa zodziwika bwino za zotumphukira za rat ratial prefrontal cortex pa amphetamine- ndi cocaine-ikiwayititsa pakulimbikitsa. Cereb Cortex 10: 488-498.

  216. ↵
    1. Ungless MA,
    2. Argilli E,
    3. Bonci A

    (2010) Zotsatira za kupsinjika ndi kupsinjika kwa ma dopamine neurons: zomwe zimapangitsa kuti munthu akhale wosokoneza. Neurosci Biobehav Rev 35: 151-156.

  217. ↵
    1. Ungless MA,
    2. Whistler JL,
    3. Malenka RC,
    4. Bonci A

    (2001) Kuwonetsedwa kamodzi kwa cocaine mu vivo kumapangitsa chidwi cha nthawi yayitali mu dopamine neurons. Nature 411: 583-587.

  218. ↵
    1. Van Bockstaele EJ,
    2. Pickel VM

    (1995) Gaba yokhala ndi ma neuroni mu projekiti ya gawo la ventral tegmental ku nucleus yomwe imakumana mu ubongo wama rat. Resin ya ubongo 682: 215-221.

  219. ↵
    1. Vanderschuren LJ,
    2. Kalivas PW

    (2000) Kusintha kwa kutuluka kwa dopaminergic ndi glutamatergic mu kutulutsidwa ndi kuwonetseratu kuchitidwa kwa khalidwe: Kuwunika kwakukulu kwa maphunziro otsogolera. Psychopharmacology (Berl) 151: 99-120.

  220. ↵
    1. Vezina P

    (1996) Kuyambitsa kwa D1 dopamine receptor ndikofunikira kuti amphetamine iyambe kukulitsa chidwi chake m'dera la ventral tegmental. J Neurosci 16:2411–2420.

  221. ↵
    1. Vezina P

    (2004) Kuchepetsa mphamvu ya midbrain dopamine neuron reactivity ndi kudzilamulira nokha kwa mankhwala othandizira a psychomotor. Neurosci Biobehav Rev 27: 827-839.

  222. ↵
    1. Vezina P,
    2. Giovino AA,
    3. RA wanzeru,
    4. Stewart J

    (1989) Kuzungulira kwachilengedwe pakati pa ma locomotor ogwiritsira ntchito morphine ndi amphetamine. Pharmacol Biochem Behav 32: 581-584.

  223. ↵
    1. Vezina P,
    2. Kalivas PW,
    3. Stewart J

    (1987) Kuchulukitsa kumachitika pazotsatira za morphine ndi chiwonetsero chogwira ntchito cha mu opioid receptor agonist, DAGO, yomwe imayendetsedwa mobwerezabwereza kumalo osungira kanthu koma osati ku ma nucleus. Resin ya ubongo 417: 51-58.

  224. ↵
    1. Vezina P,
    2. Leyton M

    (2009) Makhalidwe oyenera komanso mawu osangalatsa a nyama ndi anthu. Neuropharmacology 56 (Suppl 1): 160-168.

  225. ↵
    1. Vezina P,
    2. Lorrain DS,
    3. Arnold GM,
    4. Austin JD,
    5. Suto N

    (2002) Kupereka mphamvu kwa midbrain dopamine neuron reactivity kumalimbikitsa kufunafuna kwa amphetamine. J Neurosci 22: 4654-4662.

  226. ↵
    1. Vezina P,
    2. Stewart J

    (1990) Amphetamine yomwe imayendetsedwera kumalo osokoneza bongo koma osagwiritsa ntchito nyukiliya imamva makoswe ku systemic morphine: kusowa kwa zofunikira. Resin ya ubongo 516: 99-106.

  227. ↵
    1. Volkow ND,
    2. Fowler JS,
    3. Wang GJ

    (2004) Ubongo wa anthu omwe adawonetsedwa amawunikira pamtundu wa kafukufuku wamalingaliro: madera aubongo ndi njira zamankhwala. Neuropharmacology 47 (Suppl 1): 3-13.

  228. ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Ma Y,
    4. Fowler JS,
    5. Wong C,
    6. Ding YS,
    7. Hitzemann R,
    8. Swanson JM,
    9. Kalivas P

    (2005) Kutsegula kwa orbital komanso medial prefrontal cortex ndi methylphenidate m'maphunziro omwe ali ndi mankhwala osokoneza bongo a cocaine koma osawongolera: kufunikira kwa kusuta. J Neurosci 25: 3932-3939.

  229. ↵
    1. Wang B,
    2. Luo F,
    3. Zhang WT,
    4. Han JS

    (2000) Kupanikizika kapena kubwezeretsa mankhwala kumapangitsa kubwezeretsanso makonda m'malo momwe mungakondere. Neuroreport 11: 2781-2784.

  230. ↵
    1. Wang B,
    2. Shaham Y,
    3. Zitzman D,
    4. Azari S,
    5. RA wanzeru,
    6. Inu ZB

    (2005) Cocaine zochitika zimakhazikitsa kuwongolera kwa midbrain glutamate ndi dopamine ndi corticotropin-yotulutsa chinthu: gawo pakubwezeretsa kupsinjika kwa kufunafuna mankhwala. J Neurosci 25: 5389-5396.

  231. ↵
    1. Wang YC,
    2. Hsiao S

    (2003) Zokhudza ma Amphetamine: magawo osayanjanitsika komanso ogwirizana. Behav Neurosci 117: 961-969.

  232. ↵
    1. White FJ,
    2. Wang RY

    (1984) Umboni wa zamagetsi wa A10 dopamine autoreceptor subsensitivity kutsatira chithandizo cha d-amphetamine. Resin ya ubongo 309: 283-292.

  233. ↵
    1. White FJ,
    2. Hu HT,
    3. Henry DJ,
    4. Zhang XF

    (1995a) Neurophysiological kusintha kwa dongosolo la mesocorticolimbic dopamine ndi kayendedwe ka cocaine mobwerezabwereza, mu The Neurobiology of Cocaine: Cellular and Molecular Mechanisms (Hammer RP Jr. ed) pp 99-119, CRC Press, New York.

  234. ↵
    1. White FJ,
    2. Hu XT,
    3. Zhang XF,
    4. Wolf ME

    (1995b) Kobwerezabwereza kayendedwe ka cocaine kapena amphetamine alters neuronal mayankho ku glutamate mu machoaccumbens dopamine system. J Pharmacol Exp Ther 273: 445-454.

  235. ↵
    1. Williams JM,
    2. Steketee JD

    (2004) Cocaine imawonjezera kukhathamiritsa kwa makoswe am'kati mwa cocaine: chidwi pamaphunziro. Eur J Neurosci 20: 1639-1646.

  236. ↵
    1. Williams JM,
    2. Steketee JD

    (2005) Zotsatira zodalirika zamagetsi a cocaine mobwerezabwereza pakufalikira kwa dopamine. Neuropharmacology 48: 51-61.

  237. ↵
    1. Wolf ME,
    2. Dahlin SL,
    3. Hu XT,
    4. Xue CJ,
    5. White K

    (1995) Zotsatira za zilonda za prefrontal cortex, amygdala, kapena fornix pa khalidwe lokopa chidwi cha amphetamine: kuyerekeza ndi N -methyl-d-aspartate antagonists. Neuroscience 69:417–439.

  238. ↵
    1. Wolf ME,
    2. Xue CJ

    (1998) Amphetamine ndi D1 dopamine receptor agonists amatulutsa zotsatira za biphasic pa glutamate efflux mu malo a rat ventral tegmental: kusinthidwa ndi kubwerezedwa kwa amphetamine. J Neurochem 70: 198-209.

  239. ↵
    1. Wolf ME,
    2. Xue CJ

    (1999) Amphetamine-anachititsa glutamate efflux mdera la rat ventral gawo lotsekemera limalepheretsedwa ndi MK-801, SCH 23390, ndi zototenic acid zotumphukira. J Neurochem 73: 1529-1538.

  240. ↵
    1. Wu WR,
    2. Li N,
    3. Sorg BA

    (2003) Zotsatira zazitali za kubwereza cocaine mobwerezabwereza pamankhwala oyamba a cortex dopamine. Resin ya ubongo 991: 232-239.

  241. ↵
    1. Xi ZX,
    2. Ramamoorthy S,
    3. Baker DA,
    4. Shen H,
    5. Samuvel DJ,
    6. Kalivas PW

    (2002) Kusintha kwa gulu lachiwiri la metabotropic glutamate receptor kosonyeza cocaine wovuta. J Pharmacol Exp Ther 303: 608-615.

  242. ↵
    1. Xie X,
    2. Ramirez DR,
    3. Lasseter HC,
    4. Fuchs RA

    (2010) Zotsatira za mGluR1 antagonism mu dorsal hippocampus pazomwe zimayambitsa mankhwala-zimapangitsa kubwezeretsa mikhalidwe yofunafuna cocaine mu makoswe. Psychopharmacology (Berl) 208: 1-11.

  243. ↵
    1. Xie X,
    2. Steketee JD

    (2009a) Zotsatira zowonetsedwa kawiri kawiri pa cocaine pagulu II metabotropic glutamate receptor function mu rat medial prefrontal cortex: maphunziro aukadaulo ndi mitsempha. Psychopharmacology (Berl) 203: 501-510.

  244. ↵
    1. Xie X,
    2. Steketee JD

    (2009b) Zotsatira zowonetsedwa kawiri kawiri pa cocaine pagulu II metabotropic glutamate receptor function mu rat medial prefrontal cortex: maphunziro aukadaulo ndi mitsempha. Psychopharmacology (Berl) 203: 501-510.

  245. ↵
    1. Yamaguchi M,
    2. Suzuki T,
    3. Abe S,
    4. Hori T,
    5. Kurita H,
    6. Asada T,
    7. Okado N,
    8. Arai H

    (2002) Kubwerezabwereza kwa cocaine kumakhudza mosiyanasiyana NMDA receptor subunit (NR1, NR2A-C) mRNA mu ubongo wama rat. Synapse 46: 157-169.

  246. ↵
    1. CD Wachinyamata,
    2. Deutch AY

    (1998) Zotsatira za zotupa za thalamic paraventricular nucleus zotupa za cocaine-zomwe zimayambitsa ntchito ya phenocaotor ndi chidwi. Pharmacol Biochem Behav 60: 753-758.

  247. ↵
    1. Zapata A,
    2. Chefer VI,
    3. Ator R,
    4. Shippenberg TS,
    5. Rocha BA

    (2003) Kulimbikitsa kudzisamalira komanso kuyendetsa bwino mayankho a dopamine mu nyukiliya ikuluikulu pambuyo podziyendetsa pakokha pathupi pathupi. Eur J Neurosci 17: 590-596.

  248. ↵
    1. Zapata A,
    2. Gonzales RA,
    3. Shippenberg TS

    (2006) Kubwereza kwa ethanol kumapangitsa chidwi cha anthu osagwirizana ndi zomwe zimachitika mu C57BL / 6J ndi mbewa za DBA / 2J. Neuropsychopharmacology 31: 396-405.

  249. ↵
    1. Zhang X,
    2. Lee TH,
    3. Davidson C,
    4. Lazarus C,
    5. Wetsel WC,
    6. Ellinwood EH

    (2007) Kubweza kwa cocaine komwe kumapangitsa chidwi cha zochita za cocaine komanso phosphorylation ya NR2B ndi GluR1 subunits ya NMDA ndi AMPA receptors. Neuropsychopharmacology 32: 377-387.

  250. ↵
    1. Zhang XF,
    2. Hu XT,
    3. White FJ,
    4. Wolf ME

    (1997) Kuchulukitsa kwamphamvu kwa zotupa za malo am'kati mwa dopamine kutsetsereka pambuyo pakukonzekera mobwerezabwereza kwa cocaine kapena amphetamine kumakhala kwakanthawi komanso mosamala kumaphatikizapo ma receptors a AMPA. J Pharmacol Exp Ther 281: 699-706.

  251. ↵
    1. Zhou W,
    2. Kalivas PW

    (2008) N-acetylcysteine ​​amachepetsa kuyankha ndikuchulukitsa kupilira pakuchulukitsa kwa cue- ndi heroin-wogwiritsa ntchito mankhwala osokoneza bongo. Biol Psychiatry 63: 338-340.

 

Nkhani zomwe zikufotokoza izi

  • Chithandizo champhamvu chothandizira kusokonezeka kwa vuto la kuchepa kwa magazi ndi chiwopsezo chokhala ndi vuto la kugwiritsa ntchito mankhwala osokoneza bongo Br. J. Psychiatry Ogasiti 1, 2013 203: 112-119
  • Sensitization ya Locomotor ku Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity mu Nukola Accumbens ndikukulitsa Ethanol Kudzilamulira J. Neurosci. Marichi 13, 2013 33: 4834-4842
  • Kufufuza magawo a mphotho ya neuroanatomical kufunafuna kutsatira njira zopewera kukhala mbewa J. Physiol. Meyi 15, 2012 590: 2427-2442