Kukhudzidwa ndi zakudya zokhudzana ndi khalidwe labwino, kuwonetsetsa pamtundu wa cocaine ndi morphine, kutsekemera kwa mankhwala, komanso kudya zakudya (2006)

J Neurosci. 2006 Jul 5;26(27):7163-71.

Le Merrer J1, Stephens DN.

PMID: 16822973

DOI: 10.1523 / JNEUROSCI.5345-05.2006

Kudalirika

Kugwiritsa ntchito mankhwala osokoneza bongo mobwerezabwereza kumawonjezera mphamvu zawo ndipo kumapangitsa kuti anthu azigwiritsa ntchito mankhwala osokoneza bongo. Tidayesa ngati chakudya chimayambitsanso chimodzimodzi. Mbewa zamphongo zomwe zimasowa chakudya zimapatsidwa chakudya chatsopano pamayeso a 30 min mu runway (FR group) yomwe imayeza zochitika zapanyumba. Pomwe ntchito za gululi zidakulirakulira poyesedwa mobwerezabwereza, zomwe gulu limakumana ndi mayendedwe olowera koma omwe adalandira chakudya m khola lanyumba (gulu la FH), kapena gulu lomwe lidakhutitsidwa ndi prefeeding asanayesedwe (gulu la SAT), lidachepa. Atawonekera pamayendedwe osowa chakudya, gululi limagwira ntchito kwambiri kuposa magulu enawo (zochitika); palibe kusiyana kwa zochita komwe kunawonedwa munjira ina, yopanda chakudya, zida. Zochitika zanyumba zidapulumuka kwamasabata atatu osawonekera pamsewu. Zochita zowongoleredwa zidachepetsedwa ndi opiate antagonist naltrexone (3-10 mg / kg) komanso wotsutsana ndi AMPA receptor antagonist GYKI 20 [52466- (1-aminophenyl) -4-methyl-4-methylenedioxy-7,8H-5, 2,3-benzodiazepine hydrochloride] (5-10 mg / kg). Wotsutsana ndi D1 SCH23390 [R (+) - 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] (15-30 microg / kg ) ndi D2 antagonist sulpiride (25-125 mg / kg) adachepetsa zochitika mosasankha. Mlingo umodzi wokha wa cocaine (10 mg / kg) kapena morphine (20 mg / kg) wochulukitsa zochitika poyerekeza ndi saline, zomwe zimalimbikitsa kukhala zazikulu m'gululi la FR, kutanthauza "kulimbikitsana" ndi mankhwalawa. Komabe, kunyengerera ndi GYKI 52466 kapena naltrexone pamiyeso yomwe imapondereza zochitika mu nyama za FR kupondereza chidwi cha cocaine. Akaloledwa kutsatsa ad libitum kupeza chakudya munjira yothamanga, mbewa za FR zidadya ma pellets ambiri pamayeso ochepa. Chifukwa chake, zambiri mwazomwe zimapangitsa kuti anthu azitha kugwiritsa ntchito mankhwala osokoneza bongo atha kuwonetsedwa atagwiritsa ntchito mphotho yazakudya ndipo zitha kuchititsa kudya kwambiri.

Introduction

Mukapatsidwa mobwerezabwereza, zotsatira zolimbikitsa za mankhwala osokoneza bongo zikuwonjezeka (Eikelboom ndi Stewart, 1982; Robinson ndi Becker, 1986). Chodabwitsa ichi chikudziwika ngati khalidwe lolimbikitsa komanso lingakhale lalitali. Ochita kafukufuku amafufuza kuchitidwa molakwika monga khalidwe la pulasitiki yokhudzana ndi kugwiritsira ntchito mankhwala osokoneza bongo, poyembekeza kuti kumvetsetsa njira za neural zomwe zimayambitsa mtundu uwu wa pulasitiki kungapereke chidziwitso pa zochitika zina zapulasitiki zomwe zimayambitsa chizunzo. Chiphunzitso chimodzi cha kugwiritsira ntchito mankhwala osokoneza bongo komanso kubwerezabwereza (Robinson ndi Berridge, 1993, 2001) amachititsa kuti chidziwitso cha khalidwechi chichitike chifukwa chakuti mobwerezabwereza kumwa mankhwala osokoneza bongo kumawathandiza kufalitsa njira zowonjezera zomwe zimapangitsa kuti pakhale njira zothandizira anthu kuti azikhala ndi zofuna zawo.

Zambiri mwa zolimbikitsa za khalidwe zimawoneka kuti zikuwonetsa kukhazikitsidwa kwa mabungwe ogwirizana pakati pa mankhwala osokoneza bongo a mankhwala, ndi chilengedwe chomwe mankhwalawa amachidziwa (Stewart et al., 1984; Vezina ndi Stewart, 1984; Stewart ndi Vezina, 1988; Vezina et al., 1989; Crombag et al., 1996), kuti chilengedwe chimene mankhwala amachidziwidwa chimapangitsa ntchito ngakhale pamene palibe mankhwala osamalidwa (opangidwira ntchito)Stewart, 1983). Zimatsimikizirika kuti zochitika zachilengedwe zomwe zimapangidwira ndi zokhumba zokhumba zokhumba zowonjezera zowonjezera ntchito zolimbikitsa (Sheffield ndi Campbell, 1954; Bindra, 1968). Chifukwa mankhwala a psychostimulant ndi opiate ndi mphoto zabwino (Volkow ndi Wanzeru, 2005), chilengedwe chomwe chikugwirizana nawo chiyenera kuwonjezera ntchito. Choncho, kufotokozera kwazochitika zochitikazo ndikuti zimasonyeza ubale wokhala ndi chidziwitso cha chilengedwe ndi mankhwala, osati chiyanjano chokwanira. Pachifukwa ichi, mphotho ya mankhwala siidzayembekezereka kusiyana ndi mphoto zachilengedwe.

Nkhaniyi ikugwirizana ndi kufanana pakati pa khalidwe ndi kuphunzitsa mitundu ina, ndi syntaptic plasticity. Choncho, kupeza chidziwitso cha khalidwe ndikutetezedwa ndi mankhwala omwe akuphatikizapo antchito a NMDA (Wolf ndi Khansa, 1991; Kalivas ndi Alesdatter, 1993; Stewart ndi Druhan, 1993) ndi mapuloteni mawonekedwe a inhibitors (Karler et al., 1993) zomwe zimalepheretsa kuthekera kwanthawi yaitali ndi kuphunzira. Komanso, chifukwa dopamine ndi ntchito yake ku D1 mapulogalamu othandizira amathandizira syntaptic plastikiity (Beninger ndi Miller, 1998; Nestler, 2001), kuwonjezera kwa psychostimulant-stimulated stimulus synaptic dopamine kungathandize kupanga mapangidwe amphamvu kwambiri pakati pa reinforcer ndi chilengedwe.

Cholinga cha phunziroli chinali kuyesa ngati chakudya, mphotho yachilengedwe, chingathandize kuthandizira khalidwe mu mbewa. Tinayang'anitsitsa ntchito ya ogulitsa zakudya zamphaka zomwe zinkasowa chakudya m'mayendedwe amtundu uliwonse, ndipo amaziyerekezera ndi zinyama zomwe zimayikidwa tsiku lililonse kumalo othamanga koma popanda pellets (kuperekedwa pambuyo pake pakhomo la nyumba), kapena Zowonongeka ku pellets mu runwayways koma satiated 30 min asanayesedwe. Kufotokozera ntchito yowonongeka kwa zakudya kunayesedwa pa nkhani yeniyeni ndi moyo wautali, ndipo kuyanjana kwa njira za dopaminergic, opioid, ndi AMPA glutamatergic zinayesedwa. Kuwongolera pamtunda kwa zotsatira zoopsa za cocaine ndi morphine zinayesedwa, komanso zotsatira za naltrexone, 1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), ndi R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) polimbikitsana pamtengowo kuti ayambe kumwa mankhwala osokoneza bongo. Pomalizira, tinayesa momwe tingagwiritsire ntchito chakudya chophatikizana kuti tiyambe kudya zakudya zowonjezera zinyama.

Zida ndi njira

Ophunzira

Ophunzira anali amphongo amphongo (C57BL / 6 × SV129) anabadwira ku Dipatimenti ya Psychology ku University of Sussex ndipo anayeza 25-30 g kumayambiriro kwa mayesero. Iwo ankakhala m'magulu awiri kapena atatu pa khola pa 12 kuwala / mdima (kuyatsa pa 7 PM), kutentha kwa 19-21 ° C ndi 50% chinyezi. Mlungu umodzi usanayambe kupeza mphamvu zowonjezera chakudya, mbewazo zinali chakudya chokhalira kuchepetsa miyeso yawo ku ~90% ya kulemera kwao kwaulere. Madzi analipo ad libitum. Zomwe zinayesedwa zinavomerezedwa ndi komiti yamakhalidwe abwino ndipo zinachitidwa pansi pa malamulo a United Kingdom pa kuyesa nyama [Animal (Scientific Procedures Act), 1986].

Zida zoyesera

Zochita zowonongeka zimayang'aniridwa ndi polypropylene circular runways (mkati mwake, 11 masentimita, kutalika kwake, 25 masentimita, kutalika, 25 masentimita) okhala ndi mafano asanu ndi atatu osapangidwa ndi ma infrared omwe amagawidwa nthawi zonse ndi malo 2 masentimita pamwamba (Chakudya ndi Stephens, 1998). Chiwerengero cha kuthamanga kwazitsulo pambuyo pa kupumula katatu kotsatizana mu njira imodzi chinagwiritsidwa ntchito monga chiyero cha kutuluka kwapitali. Zina mwachindunji zinayesedwa m'mabotolo am'kati mwake [19 cm (m'lifupi) × 45 masentimita (kutalika) × 20 masentimita (kutalika)] ​​ali ndi zigawo zitatu zofanana zazing'ono zopangidwa ndi maonekedwe a 1 masentimita pamwamba pa pansi ndipo amagawanika nthawi zonse pambali pazitali zamkati. Kupititsa patsogolo ntchito kunkapezeka ngati chiwerengero cha nyama chinaphwanya mizere iwiri yotsatizana.

Yesetsani 1: kupeza chakudya chokhazikitsa chakudya

Gawo lirilonse la tsiku ndi tsiku linali ndi preexposure ya 10 min (kuyendetsa A), kenako padzakhala kupuma kwa 5 pamene nyamazo zinalowetsedwa m'nyumba zawo. Nthangazo zinabwerera kumalo othamanga kwa 20 min (kuthamanga B). Ndondomekoyi inakonzedwa kuti ikhale yovomerezeka kwambiri ndi mankhwala, pomwe nyamazo zimayamba kugwira ntchito ku malo osungirako ntchito, panthawi yoyamba, kenaka imayikidwa ndi mankhwala kapena galimotoyo ndipo imabwereranso kumagetsi kuthamangitsidwa.

Magulu atatu a nyama za 10 anapangidwa. Mgulu loyambirira (chakudya m'mayendedwe, njala: FR), zinyama zinalandira mapepala a 20 okoma (20 mg aliyense; Noyes Precision pellets, Formula P; Zakudya Zofufuzira, New Brunswick, NJ) atathamangitsidwa m'mayendedwe akabwezeredwa kuti athamangire B. Mu gulu lachiwiri (chakudya cha khomo la nyumba, njala: FH), mbewazo zinkaonekera ku mayendedwe monga gulu la FR, kupatula kuti palibe zotsekemera Pellets analipo mu zipangizo. Zilonda zokwana makumi awiri ndi ziwiri zowonjezera zimaperekedwa m'khola la nyumba 45 min pambuyo pa kutha kwa khalidwe. Gulu lachitatu (chakudya mu run runways, satiated: SAT) chinali gulu la FR, kuphatikizapo kupezeka kwa mapepala otsekemera, kupatula kuti zinyama zinasungunuka 30 min musanayambe chizolowezi chochita khalidwe pozilandira mapepala omwewo okoma ad libitum mu khola lawo la nyumba. Zinyama zonse zidadyetsedwa ndi ma laboratory oyendetsa masana (pa 3-4 PM) pa nthawi yosiyana (60-90 min) atayesedwa, kuti athetse mgwirizano pakati pa kuyesera ndi kudyetsa chakudya. Nyama sizinkazoloŵera mapepala osungunuka asanayambe kuyesedwa kuti asasokonezedwe ndi chikhalidwe chotsatira. Nyama za FR zimadya mapepala onse pamsewu pambuyo pa magawo awiri kapena atatu.

Yesetsani 2: mndandanda wa zochitika zomwe zimakhudzidwa ndi chakudya chokhudzidwa ndi zakudya

Kumapeto kwa gawo lopezapo, nyama za FR ndi ma FH zinkawonekera kumalo othamanga kapena mabokosi opangira mankhwala. Ndondomekoyi inali yofanana ndi nthawi yopeza maphunziro, kupatulapo ntchito yopita patsogolo inayesedwa pokhapokha kuti panalibe mapepala otsekemera (ntchito yosinthidwa). Pambuyo pobwezeretsa bwino chiyero chawo chogwira ntchito (magawo atatu kapena anayi opindula), zinyamazo zinabwezeretsedwanso mwa dongosolo loyenderana.

Kutalika kwa yankho lokhala ndi maganizo okhudzidwa ndi chakudya

Pambuyo pa magawo atatu kapena anayi omwe anapeza, FR ndi ziweto za FH zinayesedwa kuti zikhale zochitika pamsewu wothamanga (tsiku la 1). Palibe mapaleti okoma omwe anapatsidwa. Gawo lotsatira linali gawo lachidziwitso chodzipiritsa, mapepala okometsetsa amakhalapo. Kenaka magawo a tsiku ndi tsiku anaimitsidwa kwa masabata a 3, nyama zomwe zatsala pansi pa chakudya. Patsiku la 22, mbewazo zinatsitsidwanso kumalo othamanga popanda pellets zokometsera kuti aone zomwe zimachitika.

Yesetsani 3: zotsatira za otsutsa a dopaminergic powonetsa zochitika zokhudzana ndi zakudya

Magulu awiri a 9-10 nyama zosadziwika anazipanga (FR ndi FH magulu). Kumapeto kwa gawo lopeza, nyama izi zidayikidwa ndi D1 wotsutsa wolandira SCH23390 (pa 15 kapena 30 μg / kg, ip) kapena galimoto yotsatira mapangidwe a Latin; panalibe mapepala otsekemera omwe anapatsidwa. Zinyama zinali ndi jekeseni 5 min musanayambe kuthamanga A, kuti aone zotsatira zomwe zingatheke pa ntchito yoyembekezera. Pambuyo pa gawo lililonse loyezetsa mankhwala, zinyamazo zidaperekedwera magawo atatu kapena anayi omwe amawunikira nthawi zonse. Ena awiri FR ndi FH (n = 7-9) magulu anapangidwa kuchokera ku nyama zosamvera kuti ayese zotsatira za D2/D3 Sulpiride (25, 75, kapena 125 mg / kg) poyerekeza ndi galimoto, pogwiritsa ntchito zojambula zomwezo, kupatula kuti sulpiride inayikidwa 30 min musanayambe kuthamanga A.

Yesetsani 4: zotsatira za opiate ndi AMPA omwe amatha kutsutsa malingaliro pa zochitika zowonongeka ndi zakudya

Nkhumba za FH ndi FR zokhudzana ndi nthawi yaitali zakhala zikulowetsedweratu ndi nonselective koma anti-opiate antagonist naltrexone (10 ndi 20 mg / kg, ip) kapena galimoto, ndi mdani wa AMPA GYKI 52466 (5 kapena 10 mg / kg, ip ) kapena galimoto, motsatira chojambula cha Latin; palibe pellets zokometsetsa zomwe zinalipo panthawi ya B. Naltrexone inkaperekedwa kwa 30 min asanayambe A; GYKI 52466 inayikidwa mwamsanga nthawi yomweyo isanathamangire A chifukwa cha moyo wake waufupi. Pambuyo pa gawo lililonse la kuyezetsa mankhwala, zinyamazo zinaperekedwera magawo atatu kapena anayi omwe angapezepo nthawi zonse kuti athe kuwonetsa bwino momwe amachitira.

Yesetsani 5: zotsatira za vuto la cocaine ndi morphine

Magulu awiri a 10 nyama zamphongo zinakhazikitsidwa: gulu la FR ndi gulu la FH. Kumapeto kwa gawoli, nyamazo zimalandira vuto loyambitsa cocaine (10 mg / kg, ip) kapena jekeseni (saline) mwamsanga musanayambe B; panalibe mapepala otsekemera omwe anapatsidwa. Kuthamanga B kunangokhala 10 min. Pambuyo pokonzanso zonse zomwe zimagwira ntchito (magawo atatu kapena anai), zinyama zinabwezeretsedwanso moyenera. Mofananamo, magulu awiri ena asanu ndi atatu a FR ndi asanu ndi atatu a FF anapangidwa kuti ayese zotsatira za vuto la morphine. Pamapeto pake, nyamazo zimalandira morphine (20 mg / kg, ip) kapena injini ya saline 15 min asanayambe A; panalibe mapepala otsekemera omwe anapatsidwa. Kuthamanga B kudatenga 10 min. Pambuyo pobwezeretsa bwino msinkhu wawo wa ntchito, zinyama zinabwezeretsedwanso mu dongosolo loyendetsa bwino.

Kusintha kwake kwa zotsatira za cocaine ndi AMPA, opiate, kapena dopamine D1 otsutsa antchito

FR ndi nyama FH poyamba ankachitidwa ndi naltrexone ndi GYKI 52466 zinagwiritsidwa ntchito mu kuyesera. Pambuyo pa magawo atatu kapena anayi omwe adalandirapo, adalandira GYKI 52466 (10 mg / kg, ip) musanathamangire A motsogoleredwa ndi cocaine (10 mg / kg, ip) musanathamangire B, kapena galimoto (saline) musanathamangitsidwe A mutsogoleredwa ndi cocaine kuthamanga B; panalibe mapepala otsekemera omwe anapatsidwa. Pambuyo pobwezeretsa bwino msinkhu wawo wa ntchito, zinyama zinabwezeretsedwanso mu dongosolo loyendetsa bwino. Kenaka, anabwezeretsedwanso mofanana, koma amalandira naltrexone (20 mg / kg) kapena SCH23390 (30 μg / kg) mmalo mwa GYKI 52466. GYKI 52466 ndi SCH23390 adayikidwa jekeseni musanayambe kuthamanga A, ndipo naltrexone inkaperekedwa kwa 30 min pasanayambe kuthamanga A.

Yesani 6: kuthekera kwa malo odyetserako chakudya kuti mudye chakudya

Zinyama za FR ndi FH zomwe zidachitidwa kale ndi sulpiride adayesedwa pamayeso omwewo poyeserera, kupatula kuti kuthamanga B kunangotsala 5 min kokha komanso kuti ma pellets 80 okoma anali pamenepo. Ntchito yakutsogolo idayang'aniridwa panthawi yothamanga A ndikuyendetsa B. Kuchuluka kwa ma pellets omwe amapezeka pa mbewa iliyonse kumayesedwa isanachitike komanso itatha B (poganizira zotayika zilizonse). Kudya kwa mbewa iliyonse kumawonetsedwa m'magalamu kapena kuchuluka kwa thupi la nyama.

mankhwala

Cocaine hydrochloride, SCH23390, naltrexone (Sigma, Poole, UK), ndi morphine hydrochloride (McFarland Smith, Edinburgh, UK) adasungunuka ndi wosabala 0.9% saline ndi jekeseni intraperitoneally mu buku la 10 ml / kg. (±) Sulpiride (Tocris, Avonmouth, UK) komanso mdani wamkulu wa AMPA GYKI 52466 (IDR, Budapest, Hungary) adasungunuka pang'onopang'ono ya hydrochloric acid (0.1 m), yoyeretsedwa ndi wosabala 0.9% saline mpaka kumapeto ndi anabweretsa pH 6.5-7 ndi NaOH (1 m).

Kusanthula kusanthula

Yesani 1.

Deta zidasanthuledwa pogwiritsa ntchito ANOVAs njira ziwiri (FR, FH, SAT) monga pakati pa-phunziro, ndi gawo ngati mutu-phunziro. Pamene zotsatira zowonjezera zowonjezera zapezeka, posachedwa Kusanthula kunkachitika pogwiritsa ntchito mayeso a Wophunzira-Newman-Keuls. Kupitiliza njira imodzi YAM'MBUYO YOTSATIRA MWACHIKHALIDWE ndi gawoli mkati mwa mutu-phunziroli anawerengedwera gulu lirilonse kuti liwonetse kusintha kwa zochitika pamisonkhanoyi.

Yesani 2.

Kusiyana kwa zochitika zapakatikati pakati pamagulu a FR ndi FH m'malo osiyanasiyana adasanthulidwa pogwiritsa ntchito Student t yesetsani zitsanzo zosadziimira. Ponena za kuyesa kwa nthawi yaitali, deta idasanthuledwa pogwiritsa ntchito ANOVAs njira ziwiri monga gulu-pakati pa mutu ndi tsiku (1 kapena 22) monga mobwerezabwereza muyeso.

Zofufuza 3 ndi 4.

Deta pazochitika zosiyanasiyana zochiritsira zinagwiritsidwa ntchito pogwiritsa ntchito njira ziwiri zamagulu ndi gulu (FR, FH) monga pakati pa-phunziro, komanso mlingo ngati mobwerezabwereza. Kupitiliza njira imodzi YAM'MBUYO YOTSOGOLERA ndi gawoli mkati mwake-phunzirolo linagwiritsidwa ntchito kuyesa kusintha kwadongosolo kwa ntchito pa magawo.

Yesani 5.

Dongosolo la mankhwala osiyana linayesedwa pogwiritsa ntchito ANOVAs njira ziwiri ndi gulu (FR, FH) monga pakati pa-phunziro, ndi mankhwala kapena chithandizo chokwanira monga mobwerezabwereza.

Yesani 6.

Kusiyana kwamadyedwe pakati pa magulu a FR ndi FH m'malo osiyanasiyana kunasanthulidwa pogwiritsa ntchito Student t yesetsani zitsanzo zosadziimira.

Results

Yesani 1

Nkhumba zinaloledwa kufufuza njira zozungulira za 10 min (kuthamanga A) musanachotsedwe mwachidule kuti mulole mapepala otsekemera aziyikidwa pa msewu, ndipo kenako anabwezedwa (kuthamanga B). Monga momwe taonera Chithunzi 1A, kubwereza tsiku ndi tsiku chakudya kumalo othamanga panthawi yoyendetsa B pazithunzithunzi za 14 zomwe zinapangitsa kuti pakhale ntchito yowonjezera yowonjezera panthawi yoyendetsa A (ntchito yoyembekezera) mu gulu lomwe linalandira chakudya pa msewu pamene lidali ndi njala (FR), koma osati mu mbewa zomwe zinalandira chakudya mu khola la nyumba (FH) kapena mbewa zomwe zinadyetsedwa kudyetsa musanayambe kuyendetsa panjira (SAT) (kagulu ka gulu: F(2,26) = 6.53, p <0.01; zotsatira: F(13,338) = 3.39, p <0.0001). Pa magawo 14, zochitika zinali zazikulu mgulu la FR kuposa m'magulu onse a FH ndi SAT (posachedwa, p <0.01), chifukwa chakuchepa kwakukulu kwa zochitika pamagawo onse a FH (F(13,117) = 2.93; p <0.01) ndi SAT (F(13,104) = 2.15; p <0.05), koma osati mgulu la FR (F(13,117) = 1.37; NS).

 

Chithunzi 1. 

Kupeza zinthu zolimbitsa thupi. Kuwonetseratu tsiku ndi tsiku (masewera a 14) kuwayendetsa ndege kumabweretsa ntchito yowonjezera (amatanthawuza ± SEM) pa nthawi ya A (A) ndi kuthamanga B (B) mu nyama zanjala zomwe zimalandira mapepala otsekemera mu zipangizo (FR) (n = 10) poyerekeza ndi nyama zanjala zomwe zimalandira mapepala otsekemera m'nyumba yawo (FH) (n = 10) ndi nyama zodzaza ndi mapepala otsekemera omwe alipo ad libitum 30 min asanayesedwe (SAT) (n = 10). Kugawidwa kwa ntchitoyi kumaphatikizapo mabini a 5 min pa magawo anayi omaliza (amatanthawuza ± SEM) amasonyeza kuti ntchito yosungirako zowonjezera ikuwonjezeka pamapeto a kuthamanga B ku FH nyama zomwe zimapezeka mobwerezabwereza ku mayendedwe (C), kulungamitsa kafukufuku wosiyana wa 5 woyamba woyendetsa B (D) (*p <0.05; ∗∗p <0.01, ANOVA yotsatiridwa ndi Newman-Keuls posachedwa kusanthula).

 

Mofananamo, kupereka mapepala okometsetsa m'mathamangidwe kunachititsanso kuwonjezeka kwachitetezo pa nthawi yoyenda B mu gulu la FR, pamene ntchito inachepa mu FH ndi SAT. F(2,26) = 8.00, p <0.01; zotsatira: F(13,338) = 3.53, p <0.0001; Kuyanjana kwa G × S: F(26,338) = 3.99, p <0.0001) (Chith. 1B). Pakati pa maphunziro, ntchitoyi inali yaikulu mu gulu la FR kusiyana ndi magulu onse a FH ndi a SAT (posachedwa Vuto vs FH gulu: p <0.05; vs gulu la SAT: p <0.01), kuwonetsa kuwonjezeka kwakukulu kwamagawo mu gulu la FR (F(13,117) = 3.12; p <0.001), zambiri zomwe zimachitika patadutsa magawo atatu kapena asanu, koma kuchepa kwa FH (F(13,117) = 6.21; p <0.0001) ndi SAT (F(13,104) = 3.70; p <0.0001) magulu.

Nthawi yowona ntchito pa nthawi yoyendetsa B muzilombo mobwerezabwereza yowonekera ku mayendedwe inayesedwa mwa kuwonetsa ntchito zomwe zili mu mapepala a 5 min pa magawo anayi omaliza (11-14) (Chith. 1C). Ntchito inali yapamwamba mu ziweto za FR kusiyana ndi ziweto za FH ndi SAT (kagulu ka ntchito: F(2,26) = 7.29; p <0.01), ndi chizolowezi chowonjezeka kumapeto kwa kuthamanga (nthawi yogwira: F(2,26) = 7.01; p <0.001). Komabe, chizolowezi chotere chinafikira zofunikira pa nyama za FH zokha (F(3,27) = 5.25; p <0.01), osati mu FR (F(3,27) = 2.61; NS) kapena nyama za SAT (F(3,27) = 1.23; NS). Kusiyanitsa kwakukulu pakati pa FR ndi FH / SAT magulu anawonetsedwa panthawi yoyamba ya 5 ya B B (F(2,26) = 10.28; p <0.0001), ngakhale nthawi yomwe nyama za FR zimafunikira kudya ma pellets (ma pellets onse adadyedwa mu min3-4 min). Poganizira zotsatirazi, tidachepetsa kuwunika kwa manambala kuchokera miniti 5 yoyambirira BChith. 1D). Zilombo za FR, koma osati nyama za FH kapena SAT, zikuonetsa kuwonjezeka kwakukulu kwa ntchito zawo zogwira ntchito pa 14 magawo (kuwonjezeka kwakukulu kumachitika pa magawo atatu kapena anayi) pamene mapuloteni okometsera amapezeka panthawi ya B (zotsatira zake: F(2,26) = 8.52, p <0.01; zotsatira: F(13,338) = 5.95, p <0.0001; Kuyanjana kwa G × S: F(26,338) = 3.80, p <0.0001). Apanso, zochitika zinali zazikulu pamasamba 14 pagulu la FR kuposa m'magulu a FH ndi SAT (posachedwa tanthauzo, p <0.01). ANOVA yotsatira yomwe idawonetsa kuwonjezeka kwakukulu kwa zochitika mgulu la FR pazigawo (F(13,117) = 4.80; p <0.0001) koma kuchepa kwakukulu kwa FH (F(13,117) = 4.86; p <0.0001) ndi SAT (F(13,104) = 4.07; p <0.0001) magulu.

Yesani 2

Poyesedwa m'mayendedwe ozungulira popanda pellets zokometsera, zinyama zochokera ku gulu la FR zinali zogwira mtima kuposa zinyama za FH panthawi ya kuthamanga A (t(18) = 2.72, p <0.05; zochitika ± SEM: FH, 33.90 ± 5.84; FR, 80.60 ± 16.25), panthawi yothamanga B (t(18) = 3.39, p <0.01; zochitika ± SEM: FH, 28.10 ± 13.86; FR, 152.60 ± 34.02), ndipo makamaka, pakadutsa 5 min run B (t(18) = 4.02; p <0.01) (Chith. 2A). Poyesedwa m "maonekedwe ena (mabokosi ogwira ntchito amodzimadzimadzimodzi) omwe sankagwiritsidwa ntchito ndi chakudya, ndipo pakanakhala palibe mapepala otsekemera, nyama za FR sizinali zosiyana ndi ziweto za FH zomwe zakhala zikuchitika pakadutsa A (t(18) <1.63, NS; zochitika ± SEM: FH, 24.10 ± 4.25; FR, 44.80 ± 11.77), thamangani B (t(18) = 1.48, NS; ntchito ± SEM: FH, 39.30 ± 8.74; FR, 72.70 ± 20.87) kapena panthawi yoyamba ya 5 ya kuthamanga B (t(18) = 1.34, NS) (Chith. 2A).

 

Chithunzi 2. 

Chodziwika bwino ndi moyo wautali wa zochitika zokhudzana ndi zakudya (njira + SEM). Poyesedwa mwayendetsedwe kopanda pellets zokometsera, zinyama zimaperekedwa mobwerezabwereza zowonjezera mapepala m'munsimu (FR) (n = 10) yasonyezeratu ntchito zowonjezereka kuposa zinyama zopatsidwa pellets m'nyumba yawo (FH) (n = 10), panthawi yoyamba ya 5 ya kuthamanga B (A, kumanzere) (*p <0.05, ∗∗p <0.01, Yophunzira t mayeso). Mukayesedwa mwapadera (A, kumanja), nyama za FR sizinagwire ntchito kwambiri kuposa nyama za FH. Onani kuti masikelo ndi osiyana. Kusiyanitsa kwa ntchito zomwe zinachitikira pakati pa FR (n = 9) ndi FH (n = 10) zinyama pamtunda pa tsiku 1 (D1) idapitirira milungu yambiri ya 3 [mpaka tsiku la 22 (D22) la kusokonezeka tsiku ndi tsiku kuwonetsa zipangizo (B) (*p <0.05; ∗∗p <0.01, Yophunzira t mayeso).

 

Maphunziro a pawayendedwe a masabata a 3, kuwonjezeka kwa ntchito zogwirira ntchito pa nthawi yoyendetsa A ndi kuthamanga B zinawonetsedwa m'magulu onse a nyama, koma nyama za FR zinapitiriza kugwira ntchito kwambiri kuposa nyama za FH (ntchito ± SEM: kuthamanga A, tsiku 1, FH, 43.10 ± 7.98; 80.11 tsiku 13.08, 22 ± 64.10; FR, 12.93 ± 156.00; Run B, tsiku 39.74, FH, 1 ± 39.10; 13.34 tsiku, FH, 170.67 ± 43.26; FR, XUMUM ± 22). Njira ziwiri za ANOVA ndi gulu ndi kuyezetsa tsiku monga zinthu zinawonetsera zotsatira zazikulu za gulu (F(1,17) = 6.61, p <0.05; F(1,17) = 5.67, p <0.05, motsatana) ndi tsiku loyesa (F(1,17) = 8.28, p <0.05; F(1,17) = 8.02, p <0.05, motsatana) popanda kulumikizana kwakukulu. Mosiyana ndi izi, kusokonezedwa sikunakhudze kwambiri zochitika munthawi ya 5 min yoyendetsa B, nyama za FR zomwe zikugwirabe ntchito kuposa ziweto za FH (gulu: F(1,17) = 8.19, p <0.05; kuyesa tsiku zotsatira: F(1,17) = 2.17, NS) (Chith. 2B).

Yesani 3

Kugonjetsedwa ndi SCH23390 analibe mphamvu pachithunzi pa nthawi ya A (zotsatira zake: F(1,17) = 0.90, NS; zotsatira za mlingo: F(2,34) = 0.86, NS). Nyama za FR zinali zogwira mtima kuposa zinyama za FH pa nthawi yoyenda B (kagulu ka gulu: F(1,17) = 5.17, p <0.05), mtundu womwe sunasinthidwe ndi SCH23390 jekeseni (zotsatira za dose: F(2,34) = 2.06, NS) (Gulu 1). Izi zinkapangidwa chifukwa chosakhalapo SCH23390 zotsatira mu gulu la FR (F(2,16) = 0.32; NS), pamene kuchepa kwa ntchito kunawonetsedwa mu FH gulu (F(2,18) = 6.20; p <0.01). Kuyang'ana pa mphindi zisanu zoyambirira za kuthamanga B (Chith. 3A), Nyama za FR zinagwiranso ntchito kwambiri kuposa nyama za FH ndi SCH23390 jekeseni sizinathe kulepheretsa kusiyana kumeneku (kagulu ka zotsatira: F(1,17) = 16.51, p <0.001), ngakhale kuti pamlingo waukulu kwambiri unkachepetsa zochitika za oyendetsa (zotsatira zake: F(2,34) = 3.60, p <0.05). Izi, komabe, sizinafikire tanthauzo mu FR (F(2,16) = 2.11; NS) kapena FH (F(2,16) = 2.65; NS) gulu.

 

Onani gome ili: 

Gulu 1. 

Zotsatira za SCH23390, sulpiride, naltrexone, ndi GYKI 52466 pazochita zokhudzana ndi zakudya (zikutanthauza ± SEM) zomwe zimayesedwa panthawi yoyendetsa A ndi kuthamanga B (20 min)

 

 

Chithunzi 3. 

Zotsatira za SCH23390 (A), sulpiride (B), naltrexone (C), ndi GYKI 52466 (D) pachitetezo chochitidwa ndi zakudya (amatanthauza ± SEM). SCH23390 ndipo sulpiride sinalepheretse kuyanjana ndi chakudya pa nthawi yoyamba ya 5 yomwe imathamanga B zinyama zomwe poyamba zinkapezeka ndi mapepala otsekemera m'mphepete mwa nyanja (FR) (n = 9 pa mankhwala) poyerekeza ndi zinyama zomwe zimalandira mapepala a shuga mu khola lawo (FH) (n = 7-10 pa mankhwala). Mosiyana ndi zimenezi, chakudya chokhudzidwa ndi zakudya chinasokonezedwa pambuyo pa naltrexone kapena GYKI 52466 pretreatment mu nyama za FR (n = 8-9 pa mankhwala), pa mlingo (20 ndi 10 mg / kg, motsatira) zomwe zinalibe zotsatira pa ntchito ya basal mu FH nyama (n = 10 pa mankhwala) (*p <0.05, ∗∗p <0.01, Yophunzira t kuyesa kuyerekezera gulu la FH ndi FR pa mlingo uliwonse).

 

Ngakhale kuchuluka kwa mlingo wa sulpiride kunachepetsedwa ntchito mu mbewa zonse panthawi ya A, nyama za FR zinalibe zowonjezereka kuposa zinyama za FH (kagulu ka zotsatira: F(1,14) = 6.02, p <0.05; zotsatira za mlingo: F(3,42) = 8.32, p <0.01). Momwemonso, nyama za FR zimawonetsa zochitika zapamwamba kwambiri panthawi yothamanga B (gulu: F(1,14) = 11.72, p <0.01), ndi sulpiride prereatment, ngakhale kuchepetsa zochita ndi kuchuluka kwa mankhwala, sizinakhudze kusiyana kumeneku (kuchuluka kwa mankhwala: F(3,42) = 4.67, p <0.01) (Gulu 1). Pomaliza, panthawi yoyamba ya 5 yothamanga B kokha, mbewa za FR zinali zogwira ntchito kwambiri kuposa mbewa za FH (gulu: F(1,14) = 7.65, p <0.05), ndipo sulpiride inachepetsa zochitika za locomotor mofananamo m'magulu onse awiriwa: F(3,42) = 4.86, p <0.01) (Chith. 3B).

Yesani 4

Naltrexone pretreatment inachepetsanso ntchito zogwirira ntchito m'nthawi ya A, nyama za FR zomwe zikulephera kugwira ntchito kwambiri kuposa ziweto za FH (gulu: F(1,16) = 2.02, NS; zotsatira za mlingo: F(2,32) = 6.82, p <0.01). Mosiyana ndi izi, nyama za FR zimawonetsa zochitika zazikulu kuposa ziweto za FH panthawi yothamanga B (gulu: F(1,16) = 7.58, p <0.05), kusiyana komwe naltrexone ankakonda kupondereza (zotsatira zake: F(2,32) = 1.72, NS) (Gulu 1). Monga momwe taonera Chithunzi 3C, Nyama za FR zinali zogwira mtima kwambiri kuposa ziweto za FH pa nthawi yoyamba ya 5 ya B (gulu: F(1,16) = 11.36, p <0.01). Naltrexone imachepetsa zochitika zanyama mu nyama za FR, osakhudza zochitika za oyendetsa nyama za FH (zotsatira zake: F(2,32) = 5.74, p <0.05; Kuyanjana kwa G × D: F(2,32) = 6.09, p = 0.01). Njira yina yomwe ANOVA imasonyezera kuchepa kwadongosolo la ntchito mu ziweto za FR (F(2,14) = 6.11; p <0.05) koma sizikhala ndi zotsatirapo mu nyama za FH (F(2,18) = 0.90; NS).

Chithandizo ndi mdani wamkulu wa AMPA, GYKI 52466, amayesa kuchepetsa ntchito zogwirira ntchito m'magulu onsewa pakutha A (mphamvu ya dose: F(2,34) = 3.02, NS), FR ndi ziweto za FH zomwe zimagwira ntchito zofanana (gulu: F(1,17) = 1.37, NS). GYKI 52466 inachepetsanso ntchito zogwirira ntchito m'magulu onse awiri pa nthawi ya B, koma kuchepa kumeneku kunatchulidwa kwambiri mu FR kusiyana ndi ziweto za FH (kagulu ka zotsatira: F(1,17) = 4.06, NS; zotsatira za mlingo: F(2,34) = 9.10, p <0.001; Kuyanjana kwa G × D: F(2,34) = 3.73, p <0.05) (Gulu 1). Majekesero a GYKI 52466 omwe amachepetsedweratu m'magulu a FR pa nthawi yoyamba ya 5 ya B (Chith. 3D), popanda kusintha ntchito yogulitsa katundu mu FH nyama (gulu zotsatira: F(1,17) = 5.23, p <0.05; zotsatira za mlingo: F(2,34) = 10.30, p <0.001; Kuyanjana kwa G × D: F(2,34) = 6.43, p <0.01). ANOVA yotsatira idawonetsa kukula kwa GYKI 52466 mu nyama za FR (F(2,16) = 8.73; p <0.01) koma sizikhala ndi zotsatirapo mu nyama za FH (F(2,16) = 1.38; NS).

Yesani 5

Kuti tione ngati khalidweli limalimbikitsa kuti tizilombo toyambitsa matenda tiwonongeke, timayambitsa cocaine nthawi yomweyo musanathamangire B (Chith. 4A). Pambuyo pa jekeseni ya saline komanso popanda pellets zokometsera, nyama zochokera ku FR zinasonyeza kuchuluka kwa ntchito panthawi ya B (10 min) yokhudzana ndi HIV (mbewa zoyenera kuchita; t(18) = 2.15, p <0.05); Jekeseni wa cocaine wopititsa patsogolo ntchito, poyerekeza ndi jekeseni wa saline, m'magulu onse awiriwa, koma kuwonjezeka kwa ntchito pambuyo pa cocaine kunali kwakukulu mu FR kuposa gulu la FH. ANOVA wamagulu awiri omwe ali ndi gulu (G) ndi mankhwala osokoneza bongo (D) monga zinthu zinawulula zakukula kwa gulu (F(1,18) = 9.46; p <0.01) ndi mankhwala osokoneza bongo (F(1,18) = 23.90; p <0.001), ndikulumikizana kwakukulu kwa G × D (F(1,18) = 6.18; p <0.05).

 

Chithunzi 4. 

Zotsatira za vuto la cocaine (A) kapena morphine (B) jekeseni pamayesero okhudzidwa ndi zakudya (njira + SEM). Cocaine idayikidwa mwamsanga musanayambe kuthamanga B; Morphine inkaperekedwa kwa 15 min isanayambe kuthamanga A. Cocaine ndi morphine zinawonjezera ntchito zogwirira ntchito zinyama zonse; Komabe, zotsatira zawo zowonjezera zinkakhala zotheka kukhala ndi nyama zokhala ndi zakudya (FR) (n = 8-10), poyerekeza ndi maulamuliro (FH) (n = 8-10). Zotsatira za GYKI 52466 (C), naltrexone (D), kapena SCH23390 (E) polimbikitsana pamtengowo kuti ayambe kumwa mankhwala osokoneza bongo. GYKI 52466 inayikidwa mwamsanga musanathamanga A kapena naltrexone jekeseni 30 min isanayambe Kuthamangitsidwa kozunzikirapo mowa mwauchidakwa ku khola la FR (n = 9), ndipo ntchito sizinali zosiyana ndi ziweto za FH (n = 7). SCH23390 anachepetsa zotsatira za cocaine koma sanalepheretse kusiyana pakati pa FR ndi FH nyama (*p <0.05, ∗∗p <0.01, Yophunzira t kuyesa kuyerekezera FR ndi FH magulu onse; †p <0.05, ††p <0.01, †††p <0.001, ANOVA).

 

Kupweteka kwa morphine kwa morphine kunayesedwa ndi kupatsira morphine 15 min asanayambe A (Chith. 4B). Kupititsa patsogolo ntchito kunayambika ndi morphine pretreatment mu FR ndi ziweto za FH panthawi yoyenda A (mankhwala osokoneza bongo: F(1,14) = 10.93, p <0.01), popanda kusiyana pakati pamagulu (zotsatira zamagulu: F(1,14) = 0.11, NS; saline FH, 62.62 ± 16.49; FR, 87.50 ± 25.98; morphine FH, 210.62 ± 40.10; FR, 219.50 ± 80.34). Panthawi yoyendetsa B, vuto la morphine limalimbitsa ntchito m'magulu awiriwa poyerekeza ndi saline (mankhwala osokoneza bongo: F(1,14) = 5.10, p <0.05), ndipo zochitika zidatsalirabe kuposa nyama za FR kuposa nyama za FH (gulu: F(1,14) = 21.55, p <0.001).

Kuchita nawo chakudya chokhala ndi zakudya m'thupi mwachangu poyambitsa matenda a cocaine kunayesedwa poyesa zinyama ndi GYKI 52466 ndi naltrexone, pamitengo yomwe inavomerezedwa kuti ipewe ntchito zowonongeka m'mayesero ambuyomu, kapena SCH23390, zomwe, ngakhale pa mlingo womwe unachepetsa ntchito zokhudzana ndi dziko lonse lapansi, sankatha kupondereza ntchito yowonongeka. Kuthamanga kwa galimoto kapena GYKI 52466 sikunakhudze ntchito pa nthawi ya A, nyama za FR zomwe zikulephera kugwira ntchito kwambiri. F(1,16) = 0.23, NS; zotsatira za gulu: F(1,16) = 0.23, NS; ntchito ± SEM: FH saline, 38.20 ± 11.01; FR, 63.87 ± 24.44; GYKI 52466 FH, 51.10 ± 5.15; FR, 37.25 ± 7.54). Panthawi yoyendetsa B, chithandizo choyambitsana ndi GYKI 52466 musanathetse vuto la cocaine kusiyana ndi ntchito yomwe inachitika pambuyo poyendetsa galimoto pakati pa FR ndi FH. F(1,16) = 8.52, p = 0.01; zotsatira za gulu: F(1,16) = 8.02, p <0.05; Kuyanjana kwa P × G: F(1,16) = 11.07, p <0.001) (Chith. 4). Palibe zotsatira za galimoto zotsatizana ndi naltrexone pretreatment kapena FR kutsogolo kwa FH gulu linawonetsedwa mu zinyama panthawi yoyendetsa A (kutengeredwa: F(1,16) = 1.03, NS; zotsatira za gulu: F(1,16) = 1.18, NS; ntchito ± SEM: FH saline, 28.20 ± 7.24; FR, 58.50 ± 28.31; naltrexone FH, 27.90 ± 8.91; FR, 33.38 ± 8.31). Panthawi yoyendetsa B, zinyama za FR zidakali ndi vuto lotchedwa cotrexone chisanafike vuto la cocaine sichidawonetsetse ntchito zoposa za nyama za FH zomwe zimawoneka pambuyo poyendetsa galimoto. F(1,16) = 4.48, p = 0.05; zotsatira za gulu: F(1,16) = 7.30, p <0.05; Kuyanjana kwa P × G: F(1,16) = 7.56, p <0.05) (Chith. 4). Pomaliza, SCH23390 chithandizo choyambitsanso chinachepetsanso kuti nyama zankhaninkhani zowonongeka zimakhala zogwirizana ndi ziweto za FH pa nthawi yoyendetsa A (kutengeredwa kwachangu: F(1,16) = 13.38, p = 0.05; zotsatira za gulu: F(1,16) = 4.00, NS; Kugwirizana kwa P × G: F(1,16) = 5.77, p <0.05; zochitika ± SEM: mchere, FH, 38.20 ± 9.05; FR, 111.87 ± 30.67; GYKI 52466 FH, 25.00 ± 4.13; FR, 48.12 ± 25.86). Komabe, panthawi ya B, ngakhale SCH23390 kuchepetsa kuyankhidwa kwa cocaine m'magulu onsewa, kunalepheretsa kusiyana kwa ntchito zomwe zinagwirizanitsidwa pakati pa FR ndi FH nyama (chithandizo chokonzekera: F(1,16) = 18.46, p <0.001; zotsatira za gulu: F(1,16) = 7.77, p <0.05; Kuyanjana kwa P × G: F(1,16) = 4.05, NS) (Chith. 4).

Yesani 6

Kukwanitsa kayendetsedwe ka chakudya kumayesedwa ku FR ndi ziweto za FH powapatsa mwayi wopanga mapuloteni a 80 panthawi ya 5 min. B. Ntchito panthawi zonse A ndi B anali kuyang'aniridwa, kuyeza. Ntchito pa nthawi yoyendetsa A inali yochuluka mu ziweto za FR kusiyana ndi nyama za FH (t(14) = 2.34, p <0.05; zochitika ± SEM: FH, 88.14 ± 12.94; FR, 207.44 ± 49.33). Mosiyana ndi izi, zochitika panthawi yothamanga B (5 min), pomwe ma pellets okoma anali kupezeka ad libitum, inali yaikulu kwambiri mu FH mbewa kuposa FR mbewa (t(14) = -4.85, p <0.0001; zochitika ± SEM: FH, 24.00 ± 3.30; FR, 7.78 ± 1.49). Ntchito zochepa m'minyama ya FR zimachitika chifukwa chodya kwambiri ma pellets okoma kuposa nyama za FH, monga tafotokozera mu magalamu (t(14) = 2.70, p <0.05; kuchuluka kwake ± SEM: FH, 0.78 ± 0.1; FR, 1.08 ± 0.03) kapena kuchuluka kwa thupi lawo (t(14) = 3.58, p <0.01; kuchuluka kwa ± SEM: FH, 3.05 ± 0.45; FR, 4.77 ± 0.17).

Kukambirana

Mu phunziro lino, mbewa zosadya chakudya, mobwerezabwereza kuwonetsetsa chakudya chokoma mwachindunji, zikuwonetsa kuwonjezereka kosalekeza ndi kosalekeza kuntchito yogwira ntchito pambaliyi. Mosiyana ndi zimenezi, zinyama zomwe zimalandira chakudya pakhomo pawo, kapena zinyama zomwe zimapatsa chakudya chokwanira poyamba, zimasonyeza kuchepa kwa ntchito yochitapo kanthu pambuyo pobwereza mobwerezabwereza. Deta iyi ikufanana ndi kukula kwa khalidwe lachidziwitso pofuna kubwereza mobwerezabwereza kugwiritsa ntchito mankhwala osokoneza bongo monga cocaine. Pambuyo polimbikitsidwa, kuika makoswe pamalo odyera chakudya, ngakhale pakakhala chakudya, kunachititsa kuti ntchito ikhale yochuluka. Zowonjezera, kukula kwa zonse zomwe akuyembekezera (pa nthawi yoyendetsa A), ndipo kusagwira ntchito kwakukulu kunali kofunika kwambiri pamene nyama za FR zinayikidwa chimodzimodzi monga momwe adalandira chakudya chophatikiza mobwerezabwereza. Palibe kusiyana kwakukulu pakati pa magulu pakati pa magulu anawonetsedwa mu chikhalidwe chosiyana ndi chosadziwika.

Kwa kudziwa kwathu, zotsatira zathu ndizoyamba kulongosola kokhala ndi zowonjezereka kwa chakudya chokoma mu makoswe. Phunziro lapitalo (Schroeder et al., 2001) sankatha kuonetsetsa kuti makoswe amaloledwa kubwalo la chokoleti mobwerezabwereza. Komabe, mosiyana ndi phunziro lino, zinyama sizinkadya chakudya. Kusokoneza mphamvu zowononga kungakhale kovuta kwambiri pakukhazikitsa mphamvu zolimbikitsa chakudya. Kuletsedwa kwa zakudya kumathandizira kutumiza kwa dopaminergic, makamaka mu nucleus accumbens (Cadoni et al., 2003; Carr et al., 2003; Haberny et al., 2004; Lindblom et al., 2006), ndipo kumaonjezera zopindulitsa ndi zochititsa chidwi za dopamine receptor agonists (Carr et al., 2001) komanso mankhwala osokoneza bongo (Deroche et al., 1993; Bell et al., 1997; Cabeza de Vaca et al., 2004). Kuwunikira kwa kutumiza kwa dopaminergic mu nucleus accumbens, ndi mapulasitiki mu njira zogwirizana (Haberny et al., 2004; Haberny ndi Carr, 2005) kungakhale chofunikira chokhazikitsa kukhazikitsa mphamvu kwa chakudya.

Kuyerekeza kwa kuchenjezedwa kwa zakudya ndi kulimbikitsa khalidwe kwa mankhwala osokoneza bongo kumatulutsa zinthu zambiri zomwe zimagwiridwa. Kukulimbikitsani khalidwe ndi mankhwala osokoneza bongo kumapitirira miyezi ingapo chithandizo chitatha (Paulson et al., 1991; Wogulitsa ndi Goldman-Rakic, 1999). Mu phunziro lino, zonse zowonongeka ndi kuwonetsetsa kuti chakudya chokwanira ndi chakudya chapatsidwa mphoto chinapitilira pa nthawi ya masabata a 3 popanda kuwona malo odyetsera chakudya, kusonyeza kuti mayankho onse awiriwa anali odalirika. Sitinayambe nthawi yayitali.

Tikawona kuti zolembedweramo chakudya zimakhala ndi mphamvu yokweza yankho lokhazikika lokhazikika mogwirizana ndi zochitika (Bindra, 1968) zomwe zowonongeka za chilengedwe zomwe zimagwirizanitsidwa ndi zikuluzikulu zapamwamba zimalimbikitsa ntchito yogulitsa, zotsatira zomwe zatsimikiziridwa mobwerezabwereza (Jones ndi Robbins, 1992; Hayward ndi Low, 2005; Barbano ndi Cador, 2006). Kuwonjezera apo, ntchito yopanga zogwirira ntchitoyi inkawonetsedwa pamtundu wodyetsa zakudya zomwe zimayikidwa pazigawo za chakudya pamene chakudya sichinatuluke, chinali chofanana ndi kukula kwa ntchito yomwe anayeza pamene chakudya chinalipo. Chotsatira ichi chimasonyeza kuti ntchito yolimbikitsidwa yopanga zosangalatsa yomwe ikuwonetsedwa poyang'anira chakudya inali yankho lovomerezeka ku chilengedwe, kusiyana ndi limodzi loperekedwa ndi chakudya.

Kukhazikitsidwa kwa chidziwitso cha khalidwe ndi chizoloŵezi choyambitsa mankhwala kumadalira njira zogwirizana ndi zomwe zimakhalapo panthawi yaitali, chifukwa zowonongekazi zimatsekedwa ndi antchito a NMDA, mapuloteni a inhibitors, ndi dopamine D1 otsutsa. Njira zofananazi sizikufunikira kwenikweni kuti ziwonetsedwe za zolimbikitsa kapena zochitika, zomwe zikuwoneka kuti sizidalira kwambiri D1 Njira zothandizira (Beninger ndi Hahn, 1983; Cervo ndi Samanin, 1996; McFarland ndi Ettenberg, 1999). Komabe, kufotokoza kwa cues predictive kwa sucrose kupezeka kumabweretsa dopamine kumasulidwa mu nucleus accumbens (Roitman et al., 2004), kutanthawuza udindo womwe ungawathandize kupezeka kwa dopamine m'matangidwe okhudzidwa ndi zakudya. Mu phunziro lino, ngakhale D1 wotsutsa SCH23390 kapena D2/D3 Sulpiride wotsutsa anatsutsa mosamalitsa mawu a locotion conditioned, pa mlingo umene kale ankafuna kuchepetsa ntchito basal. Choncho, kuyambitsidwa kwa D1 ndi D2/D3 zovomerezeka zingagwire ntchito yosafunika kwenikweni powonetsa ntchito yowonjezera chakudya, monga momwe ntchito yogwiritsira ntchito mankhwala.

Kugonjetsedwa ndi opiate wotsutsa naltrexone kunathetsa ntchito zogwiritsira ntchito zakudya m'zilombo za FR, pamene zinalibe zochepa pazochita zowonongeka, kutanthauza kuti opioid receptors amathandizira powonetsa kuchepa kwa zakudya. Sitikudziwa deta potsatira zotsatira zowonongeka kwa opioid poyamikira cocaine, ngakhale naltrexone imalepheretsa kufotokoza khalidwe lachidziwitso kwa methamphetamine (Chiu et al., 2005). Kukhoza kwa wotsutsa wina wa opioid, naloxone, kuti achepetse kuyankhidwa kwa opaleshoni kwa othandizira chakudya (Galasi et al., 1999) komanso ntchito yokonza chakudya pamaso pa chakudya (Hayward ndi Low, 2005), komanso luso la μ-agonist morphine kuti liwonetsetse chikhalidwe chodalira-kudalira kudya (Kelley et al., 2000) limapereka udindo wa opiate receptors mu mayankho okondweretsa chakudya.

Kupititsa patsogolo ndi kufotokoza kwa cocaine-drivenduced behavioral sensitization kumakhudzidwa ndi kusintha kosokoneza ubongo (Wolf, 1998; Vanderschuren ndi Kalivas, 2000). Pakati pa malo otchedwa glutamate receptors, mapulogalamu a AMPA amawoneka kuti akugwira ntchito mwachindunji poletsa ntchito yowonongeka ndi mankhwala osokoneza bongo (Pierce et al., 1996; Chimanga ndi Kalivas, 2001; Carlezon ndi Nestler, 2002; Boudreau ndi Wolf, 2005), ndi NBQX otsutsa mpikisano wa AMPA [2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) -quinoxaline] ndi DNQX (6,7-dinitroquinoxaline-2,3-dione) ntchito yotetezera amphetamine ndi cocaine mu mbewa (Cervo ndi Samanin, 1996; Chakudya ndi Stephens, 1998; Mead et al., 1999). Mu makoswe, GYKI 52466 yemwe amatsutsana ndi AMPA omwe amalephera kulandira mankhwalawa amalepheretsa kufotokozera moyenera mankhwala a cocaine (Hotsenpiller et al., 2001). Phunziroli, GYKI 52466 inachotsa ntchito zokhudzana ndi zakudya, popanda kutsogolera zochita zokha (panthawi yoyamba ya 5 ya B-B), kutanthauza kuti ntchito yowonjezera chakudya, monga ntchito yogwiritsira ntchito mankhwala osokoneza bongo, imadalira kuyambitsidwa kwa AMPA zovomerezeka.

Nyama zikayamba kulangizidwa ndi mankhwala amodzi, nthawi zambiri zimasonyeza kusamalitsa kwa mankhwala ena (Vezina et al., 1989). Pakafukufuku wapano, kuthekera kwa cocaine ndi morphine kukulitsa zochitika za locomotor kunalimbikitsidwa kwambiri mwa nyama zolimbikitsidwa ndi chakudya, poyerekeza ndi gulu lolamulira. Ngakhale kuyankha kowonjezeraku kumatha kufotokozedwa ngati kulimbikitsana, nkhani ina ndikuti mphamvu ya cocaine kapena morphine yolimbikitsira ntchito imawoneka mosavuta ngati nyama zikuwonetsa kale kukokomeza m'malo ophatikizika ndi chakudya (Stephens ndi Mead, 2004). Komabe, chifukwa poyesa kukambirana, kuyang'ana kwa amphetamine kumayambitsa kulimbikitsana kwa munthu wogwira ntchitoyo kumalimbikitsa zakudya (Jones et al., 1990; Avena ndi Hoebel, 2003), nkutheka kuti kugwirizanitsa nkhani ndi mankhwala kapena zotsatira za zakudya kumathandizira kuwonetsa njira zomwe zimagwirizana.

Kulimbikitsidwa kwa makhalidwe kungathe kuonedwa ngati zotsatira za maphunziro othandizira anthu okhudzana ndi mankhwala osokoneza bongo. Malingaliro awa, kulamulira mobwerezabwereza kwa mankhwala m'dongosolo lomwelo kumapangitsa kuti zikhale zofunikira kuti zikhale ndi zofunikira za (CS), pamene mankhwalawa amachititsa kuti asakondwere. Kufotokozera kwa CS yekha (nkhaniyo) ndiye kumakhala kokwanira kuyambitsa yankho lovomerezeka ndi mankhwala. Chifukwa chiyanjano cha chilengedwe ndi mphotho chiyenera kuphunzitsidwa, kuphunzira, m'malo mowa mankhwala, kumapangitsa kuti anthu azikhala olimbikitsa khalidwe (Tilson ndi Rech, 1973; Pert et al., 1990). Zogwiritsidwa ntchito ndi zovuta za kuwonetsa mtanda, nkhaniyi imaneneratu kuti mankhwala osokoneza bongo omwe amaletsa kufotokozera ntchito zowonongeka ayenera kuchititsanso kuponderezana ndi zopindulitsa zina. Tinayeseratu kuneneratu kwa nyama izi, pogwiritsa ntchito GYKI 52466 ndi naltrexone musanawawonetsere ku cocaine. Zotsatira zonsezi zimapangitsa kuti chisamaliro chisokonezeke chifukwa cha cocaine. Mosiyana ndi zimenezi, kudzipatulira SCH23390, yomwe inalepheretsa kugwira ntchito zolimbitsa thupi muzilombo za FR, kuchepetsa ntchito yogulitsa katundu m'magulu onse awiriwa, koma inalephera kuthetsa mphamvu zolimbana ndi matendawa. Choncho, kuwonetsetsa mtanda kwa cocaine zomwe zimapezeka m'minyama yokhala ndi zakudya zimasonyeza zotsatira zoopsa za mankhwalawa pofotokoza momwe angayankhire pa malo odyetserako chakudya.

Zonse pamodzi, zotsatira zake zikuwonetsa kuti kuchepetsa khalidwe labwino kumachitika osati mankhwala osokoneza bongo, komanso mphotho ya chilengedwe, chakudya, komanso kuti mitundu iyi yothandizira ili ndi mbali zambiri. Dera limodzi, deta yamakono ikuwonetsa kuti kuthekera kwa mphotho zakuthupi kumathandizira kuchitapo kanthu ndikulimbikitsana kungachititse kuti phindu likhale lolimbikitsana pofuna kulimbikitsa chakudya. Komanso, angapereke yankho la funso loti chifukwa chiyani kufunafuna mankhwala kumayambitsa khalidwe, mwanjira yomwe mphotho yowonjezera siifuna (Robinson ndi Berridge, 1993, 2001), sagwiritsira ntchito mankhwala osokoneza bongo kuti athe kulimbikitsa khalidwe.

Pomalizira, tinapempha ngati chikhalidwe cha chakudya chomwe chimapangitsa kuti chilengedwe chiwonjezeke, chikhoza kuwonanso khalidwe la kudya. Dothi losavuta kapena lowala, lopangidwa ndi chakudya pamene makoswe ndi chakudya chochotsedwa, kenaka amapereka chakudya (Petrovich et al., 2002; Holland ndi Petrovich, 2005); Mofananamo, mbewa zowonjezera chakudya zimadya chakudya chochuluka kuposa zida zolimbana ndi magulu omwe ali ndi zofanana ndi zomwe zimachitika panyumba. Momwemo, chilengedwechi chinapangidwanso chakudya, mwina pogwiritsa ntchito ma CSs kuti athandize amygdala kuchoka ku hypothalamus kudzera mwa accumbens ndi prefrontal cortex (Petrovich et al., 2005). Kaya zonse zowonjezera ntchito zowonjezera komanso kulimbikitsa kudalira zimadalira maulendo ozungulira, ndipo ngati izi ndi zofanana ndi madera oyang'aniridwa panthawi yolimbikitsa khalidwe ndi mankhwala ndi funso lochititsa chidwi.

Mawu a M'munsi

  • Adalandira December 15, 2005.
  • Kukonzanso kunalandira May 26, 2006.
  • Yavomerezedwa May 27, 2006.

  • Tikuthokoza Robin Phillips, Chiara Giuliano, ndi Rosie Pyper kuti athandizidwe poyesera ndi Pete Clifton kuti athandize ndemanga zothandiza pamndandanda wa zolembazi.

  • Mndandanda wa makalata uyenera kutumizidwa kwa David N. Stephens, Dipatimenti ya Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK. Imelo: [imelo ndiotetezedwa]

Zothandizira

  1. ↵
    Avena NM, Hoebel BG (2003) Zakudya zomwe zimalimbikitsa kugonjera shuga zimachititsa kuti thupi likhale lochepa kwambiri pa amphetamine. XMUMX: 122-17.
  2. ↵
    Barbano MF, Cador M (2006) Kusiyanitsa zosiyana siyana, zolimbikitsa ndi zoyembekezera zomwe zimayambitsa khalidwe la kudya ndi mankhwala a dopaminergic ndi opioidergic. Neuropsychopharmacology 31: 1371-1381.
  3. ↵
    Bell SM, Stewart RB, Thompson SC, Meisch RA (1997) Kunyalanyaza chakudya kumapangitsa kuti malo otukuka ndi mankhwala a cocaine azikhala okonzeka komanso ochita malonda pa makoswe. Psychopharmacology 131: 1-8.
  4. ↵
    Beninger RJ, Hahn BL (1983) Pimozide amatseka malo koma osati maonekedwe a malo omwe amadziwika ndi amphetamine. Sayansi 220: 1304-1306.
  5. ↵
    Beninger RJ, Miller R (1998) Dopamine D1-monga receptors ndi maphunziro othandizira okhudzidwa ndi mphoto. Neurosci Biobehav Rev 22: 335-345.
  6. ↵
    Bindra D (1968) Kutanthauzira kwapadera kwa zotsatira za kuyendetsa ndi kuwalimbikitsa-zomwe zimakhudza zochita ndi zochita. Psychol Rev 75: 1-22.
  7. ↵
    Boudreau AC, Wolf ME (2005) Kulimbikitsidwa kwa chikhalidwe cha cocaine kumagwirizanitsidwa ndi kuwonjezeka kwa pamwamba pa AMPA pamtundu wa phokoso pamwamba pa nucleus accumbens. J Neurosci 25: 9144-9151.
  8. ↵
    Cabeza de Vaca S, Krahne LL, Carr KD (2004) Pulogalamu yowonjezereka ya kuyerekezera kudzikakamiza mu makoswe amasonyeza kuwonjezeka kwakukulu kwa mphotho ya d-amphetamine chifukwa choletsa zakudya koma palibe zotsatira za "kutsimikizira" regimen ya d-amphetamine. Psychopharmacology 175: 106-113.
  9. ↵
    Cadoni C, Solinas M, Valentini V, Di Chiara G (2003) Chisankho chokhazikitsa mtima poletsa chakudya: Kusiyanasiyana kwa kusintha kwa chigwirizano ndi dopamine. Eur J Neurosci 18: 2326-2334.
  10. ↵
    Carlezon WA Jr, Nestler EJ (2002) Mipiringi yambiri ya GluR1 mkatikatikati: chomwe chimayambitsa kulandira mankhwala osokoneza bongo? Zojambula Neurosci 25: 610-615.
  11. ↵
    Carr KD, Kim GY, Cabeza de Vaca S (2001) Zopindulitsa komanso zowonongeka zowonongeka kwa odwala opatsirana pogwiritsa ntchito dopamine amachulukitsidwa ndi zakudya zowonongeka m'makoswe. Psychopharmacology 154: 420-428.
  12. ↵
    Carr KD, Tsimberg Y, Berman Y, Yamamoto N (2003) Umboni wa kuwonjezeka kwa dopamine receptor kuzindikiritsa makoswe oletsa chakudya. XMUMX: 119-1157.
  13. ↵
    Castner SA, Goldman-Rakic ​​PS (1999) Zotsatira za psychotomimetic zotalika za mankhwala omwe amapezeka mobwerezabwereza amphetamine mu rhesus monkeys. Neuropsychopharmacology 20: 10-28.
  14. ↵
    Cervo L, Samanin R (1996) Zotsatira za otsutsa a dopaminergic ndi a glutamatergic pa kukhazikitsidwa ndi kufotokozedwa kwa mavitamini omwe amagwiritsidwa ntchito kuti azikhala ndi poizoni. Ubongo Res 731: 31-38.
  15. ↵
    Chiu CT, Ma T, Ho IK (2005) Kutsekedwa kwa mankhwala a methamphetamine omwe amachititsa kuti azikhala ndi khalidwe labwino mu makoswe ndi kayendedwe kake ka naltrexone. Chigoba Chofufumitsa Bongo 67: 100-109.
  16. ↵
    Chimanga JL, Kalivas PW (2001) Chikoka cha Cocaine ndi chikhumbo: maudindo osiyanasiyana a dopamine ndi glutamate mu nucleus accumbens. J Addict Dis 20: 43-54.
  17. ↵
    Crombag HS, Badiani A, Robinson TE (1996) Amadziwika kuti alibe amphetamine osagwiritsidwa ntchito mwamphamvu: kusiyana kwakukulu mukumvetsera kovuta kwa maganizo ndi kuwalimbikitsa. Ubongo Res 722: 227-231.
  18. ↵
    Deroche V, Piazza PV, Casolini P, Le Moal M, Simon H (1993) Kuzindikira mphamvu za maganizo za amphetamine ndi morphine zomwe zimapangitsa kuti zakudya zisamangidwe zimadalira khungu la corticosterone. Ubongo Res 611: 352-356.
  19. ↵
    Eikelboom R, Stewart J (1982) Kukonzekera kwa mankhwala opangidwa ndi mankhwala osokoneza bongo. Psychol Rev 89: 507-528.
  20. ↵
    Galasi MJ, Billington CJ, Levine AS (1999) Opioids ndi kudya kwa chakudya Neuropeptides 33: 360-368.
  21. ↵
    Haberny SL, Carr KD (2005) Kulepheretsa chakudya kumawonjezera calcium-calmodulin kinase II yomwe imalandira mpata wa NMDA / receptor / extracellular-controlled kinase 1 / 2-mediated cyclic AMP yothandizira pulophorylation yomwe imapanga pulogalamu ya D-1 dopamine zokopa zakululu mu makoswe. XMUMX: 132-1035.
  22. ↵
    Haberny SL, Berman Y, Meller E, Carr KD (2004) Kugonjetsa zakudya zowonjezera kumawonjezera D-1 dopamine receptor phosphorylation ya phospholarlar-kinified regimen 1 / 2 ndi mapuloteni othandizira mapuloteni a AMP mu caudate-putamen ndi nucleus zimagwedezeka. XMUMX: 125-289.
  23. ↵
    Hayward MD, Low MJ (2005) Kuponderezedwa kwa Naloxone kochita modzidzimutsa komanso kogwiritsa ntchito chakudya kumachepa mu mbewa zosowa dopamine D2 receptor kapena enkephalin. Ubongo Res Mol Ubongo Res 140: 91-98.
  24. ↵
    Holland PC, Petrovich GD (2005) Ma neural systems akufufuza za kuthekera kwa kudyetsa ndi zokakamiza. Physiol Behav 86: 747-761.
  25. ↵
    Hotsenpiller G, Giorgetti M, Wolf ME (2001) Kusinthasintha kwa khalidwe komanso kuthamanga kwa glutamate kumapereka chisonyezo chokhudzana ndi cocaine. Eur J Neurosci 14: 1843-1855.
  26. ↵
    Jones GH, Robbins TW (1992) Kusiyanasiyana kwa mesocortical, mesolimbic, ndi mesostriatal dopamine kutaya ntchito yokhazikika, yovomerezeka, komanso yogwiritsa ntchito mankhwala osokoneza bongo. Pharmacol Biochem Behav 43: 887-895.
  27. ↵
    Jones GH, Marsden CA, Robbins TW (1990) Kuwonjezeka kwa mphamvu ya amphetamine ndi zotsatira zokhudzana ndi mphoto zotsatizana ndi anthu omwe amadzipatula pa makoswe: zotha kusokonezeka kwa njira zodalira dopamine za nucleus accumbens. Psychopharmacology (Berl) 102: 364-372.
  28. ↵
    Kalivas PW, Alesdatter JE (1993) Kuphatikizidwa kwa N-methyl-d-aspartate kukakamiza kulandirira m'dera la ventral tegmental ndi amygdala mu chidziwitso chokhwima. J Pharmacol Exp Ther 267: 486-495.
  29. ↵
    Karler R, Finnegan KT, Calder LD (1993) Kutsekedwa kwa khalidwe lolimbikitsa kuti cocaine ndi amphetamine ndi mavitamini a mapuloteni. Ubongo Res 603: 19-24.
  30. ↵
    Kelley AE, Bakshi VP, Fleming S, Holahan MR (2000) Kusanthula zakuthupi za magawo omwe amachititsa kuti azidyetsa chifukwa chotsitsimutsa opioid ya nucleus accumbens. Neuropsychopharmacology 23: 465-467.
     
  31. ↵
    Lindblom J, Johansson A, Holmgren A, Agogo E, Nedergard C, Frederiksson R, Schiöth HB (2006) MRNA ikuwonjezeka kwambiri ya tyrosine hydroxylase ndi dopamine wonyamulira mu VTA ya ziphuphu zamphongo pambuyo pa zakudya zowonongeka. Eur J Neurosci 23: 180-186.
  32. ↵
    McFarland K, Ettenberg A (1999) Haloperidol samalepheretsa kukonda malo kapena malo opangira chakudya kapena heroin-predictive discriminative cues. Pharmacol Biochem Behav 62: 631-641.
  33. ↵
    Pambuyo pa AN, Stephens DN (1998) AMPA-receptors amagwiritsidwa ntchito pofotokozera amphetamine-induced behavioral sensitization, koma osati m'mawonedwe a zochita za amphetamine zomwe zimakhudzidwa ndi makoswe. Neuropharmacology 37: 1131-1138.
  34. ↵
    Yambani AN, Vasilaki A, Spyraki C, Duka T, Stephens DN (1999) AMPA-receptor kulowerera mu c-fos kufotokozera m'magulu a mapepala oyandikana nawo amygdala ndipo amygdala amalekanitsa magawo a neural a ntchito yogwirizanitsa ndi mphoto yabwino. Eur J Neurosci 11: 4089-4098.
  35. ↵
    Nestler EJ (2001) Makhalidwe a maselo a pulasitiki omwe akhalapo kwa nthawi yaitali. Nat Rev Neurosci 2: 119-128.
  36. ↵
    Paulson PE, Camp DM, Robinson TE (1991) Nthawi yowonongeka kwa khalidwe lachizoloŵezi ndi kulimbikitsanso khalidwe lopitirira poyerekezera ndi chigawo cha ubongo monoamine pa nthawi ya amphetamine kuchotsa makoswe. Psychopharmacology (Berl) 103: 480-492.
  37. ↵
    Powonjezera A, Post R, Weiss SR (1990) Kulemba ngati chinthu chodziwika bwino cholimbikitsidwa chochititsidwa ndi matenda opatsirana pogonana. NIDA Res Monogr 97: 208-241.
  38. ↵
    Petrovich GD, Setlow B, Holland PC, Gallagher M (2002) Amygdalo-hypothalamic circuit amavomereza mfundo zomwe zimapangitsa kuti anthu azikhala osangalala komanso azilimbikitsa kudya. J Neurosci 22: 8748-8753.
  39. ↵
    Petrovich GD, Holland PC, Gallagher M (2005) Amygdalar ndi zoyendetsa njira zowonjezera hypothalamus zimayambitsidwa ndi chidziwitso chomwe chimapangitsa kudya. J Neurosci 25: 8295-8302.
  40. ↵
    Pierce RC, Bell K, Duffy P, Kalivas PW (1996) Kocaine yomwe imabwerezedwa nthawi zambiri imapangitsa kuti amino acid isatengeke pamtundu womwe umakhalapo pang'onopang'ono. J Neurosci 16: 1550-1560.
  41. ↵
    Robinson TE, Becker JB (1986) Kusintha kwa ubongo ndi khalidwe lopangidwa ndi maulamuliro amthetamine osatha: kupenda ndi kuyesa zitsanzo zamtundu wa amphetamine psychosis. Ubongo Res 396: 157-198.
  42. ↵
    Robinson TE, Berridge KC (1993) Maziko osokoneza bongo a chilakolako cha mankhwala: chidziwitso cholimbikitsana cha kuledzera. Ubongo wa Ubongo Ubongo 18: 247-291.
  43. ↵
    Robinson TE, Berridge KC (2001) Kulimbikitsana ndi kuledzera. 96: 103-114.
  44. ↵
    Roitman MF, Stuber GD, Phillips PE, Wightman RM, Carelli RM (2004) Dopamine amagwira ntchito monga subsecond woyang'anira chakudya. J Neurosci 24: 1265-1271.
  45. ↵
    Schroeder BE, Binzak JM, Kelley AE (2001) Chizoloŵezi chofanana cha prefrontal cortical activation pambuyo poyang'ana ku chikonga kapena chokoleti chokhudzana ndi zizindikiro zamkati. XMUMX: 105-535.
  46. ↵
    Sheffield FD, Campbell BA (1954) Udindo wochita zochitika pamodzi pa makoswe anjala. J Comp Physiol Psycholo 47: 97-100.
  47. ↵
    Stephens DN, Mead AN (2004) Khalidwe lapulasitiki-limasinthidwa kusintha kwa mankhwala. Ndemanga pa mankhwala a Badiani ndi a Robinson omwe amachititsa mankhwala osokoneza bongo a neurobehavioral: udindo wa chilengedwe. Behav Pharmacol 15: 377-380.
  48. ↵
    Stewart J (1983) Zotsatira za mankhwala ndi zosavomerezeka zowonongeka pobwezeretsa opiate ndi mankhwala osokoneza bongo. Prog Neuropsychopharmacol Nthenda ya Psychiatry 7: 591-597.
  49. ↵
    Stewart J, Druhan JP (1993) Kupititsa patsogolo zikhalidwe zonse komanso kuwonetsa zotsatira za khalidwe la amphetamine kumatsekedwa ndi wotsutsana ndi MM-801 omwe alibe mpikisano. Psychopharmacology (Berl) 110: 125-132.
  50. ↵
    Stewart J, Vezina P (1988) Kuyerekezera zotsatira za intra-accumbens jekeseni wa amphetamine ndi morphine pobwezeretsanso khalidwe la heroin lodzikonda. Ubongo Res 457: 287-294.
  51. ↵
    Stewart J, wa Wit H, Eikelboom R (1984) Udindo wa zosavomerezeka ndi zovomerezeka zowonongeka mwazidziwitso muzodzilamulira za opiates ndi zosangalatsa. Psychol Rev 91: 251-268.
  52. ↵
    Tilson HA, Rech RH (1973) Chidziwitso choyamba cha mankhwala ndi zotsatira za amphetamine pa nthawi ya khalidwe. Pharmacol Biochem Behav 1: 129-132.
  53. ↵
    Vanderschuren LJ, Kalivas PW (2000) Kusintha kwa kutuluka kwa dopaminergic ndi glutamatergic mu kulembedwa ndi kufotokoza kwa chidziwitso cha khalidwe. Psychopharmacology (Berl) 151: 99-120.
  54. ↵
    Vezina P, Stewart J (1984) Kulimbitsa thupi ndi kuikapo padera kuwonjezeka kwa ntchito yomwe Morphine amachita mu VTA. Pharmacol Biochem Behav 20: 925-934.
  55. ↵
    Vezina P, Giovino AA, Wise RA, Stewart J (1989) Kuwonetsetsa bwino pakati pa malo omwe amachititsa kuti morphine ndi amphetamine ayambe kugwira ntchito. Pharmacol Biochem Behav 32: 581-584.
  56. ↵
    Volkow ND, Wwanzeru RA (2005) Kodi mankhwala osokoneza bongo angatithandize bwanji kumvetsa kunenepa kwambiri? Nat Neurosci 8: 555-560.
  57. ↵
    Wolf ME (1998) Udindo wa zokondweretsa amino acid mu chidziwitso cha khalidwe ndi maganizo opatsa mphamvu. Prog Neurobiol 54: 679-720.
  58. ↵
    Wolf ME, Khansa MR (1991) Ulamuliro wambiri wa MK-801 umapangitsa kuti anthu azidzidzidzimutsa koma amachititsa kuti amphetamine azikhala olimbikitsidwa. Ubongo Res 562: 164-168.