Izikhukhula zokuqothula ngenxa yokwesaba nokulutha kwezidakamizwa zihamba nge-prefrontal cortex (i-2009)

Ukulawulwa kwangaphambili kokuqothulwa kokwesaba okunesimo

Ubufakazi bokuqala bokuthi i-cortex yangaphambili ingahle ibe yindawo ebucayi yokuqothulwa kwesaba okunempilo kwaba ukubona ukuthi izilonda zangaphambili ziholele ekusweleni kokuqothuka (Morgan et al. I-1993; ISotres-Bayon et al. I-2006). Ngokukhethekile, ukwahlukaniswa kwe-ventral kwe-rodent medial prefrontal cortex, ebizwa ngokuthi yi-infralimbic cortex (IL-mPFC), yayibangela lo mphumela (UMorgan noLeDoux 1995; I-Fig. 1). Kusukela lapho, ubufakazi bokuqongelela buye baphakamisa ukuthi i-plastiki e-IL-mPFC ibalulekile kwimemori yokuqothula. Amaprotheni synthesis inhibitors (Sstrong et al. I-2004), IMAKK inhibitors (Huges et al. I-2004), I-NMDA receptor blockers (I-Burgos-Robles et al. I-2007; ISotres-Bayon et al. I-2008) noma ama-inactivator we-pharmacological (ISierra-Mercado et al. I-2006) injeke endaweni yangakini kwi-IL-mPFC iphazamisa amandla okuthi kamuva ikhumbule ukuqothuka. Lezi datha zisekela umbono osekuphele isikhathi eside wokuthi ukufunda okuqothulayo kudala inkumbulo yokuvimba inkumbulo ehlukile kulokho okwenziwe ngumbandela (I-Konorski 1967; I-Rescorla 2004).

 

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Umfanekiso we-1. 

Izifunda ezi-Dorsal ngokuqhathanisa nezindawo ezingena ngaphakathi kwe-rodent medial predomal cortex ngokwehlukana zilawula ukwesaba nokufuna izidakamizwa. Ukuhlukaniswa okune okukhulu kwe-rodent medial predomal cortex kuboniswe eceleni kwemingcele ye-Paxinos neWatson anatomical (3.0 mm anterior to bregma) (UPaxinos noWatson 2005). Umsebenzi esifundeni se-prelimbic (PL) ukhuthaza ukuvezwa kokwesaba okunesimo nokuziphatha okufuna i-cocaine. I-Dorsal to PL yi-dorsal anterior cingrate cortex (ACd), engahle ikhuthaze ukwesaba nokufuna izidakamizwa. I-infralimbic (IL) cortex, elele ngaphakathi ku-PL, ikhuthaza ukuqothulwa kokwesaba okunesimo kanye nokuziphatha okufuna i-cocaine. I-ventral-most dorsopeduncular cortex (DP) ingahle ifane ne-IL ekhweni lokuvimbela ukwesaba nokufuna izidakamizwa. Ngakho-ke, izifunda ezi-dorsal ze-medial predomal cortex zikhulisa ukwesaba nokufuna izidakamizwa (imicibisholo up), ngenkathi izifunda zangaphakathi zinomthelela ohlukile ekuziphatheni, kunciphisa ukwesaba nokufuna izidakamizwa (imicibisholo phansi).

Umsebenzi ku-IL-mPFC ungumlamuleli obalulekile wememori yokuvinjezelwa engaphansi kokuqothulwa. Ukuqoshwa kwe-single-unit kuveze ukuthi ukuphendula kwe-CS kuma-neurons we-IL-mPFC kuba kuphela ngemuva kokufunda kokuqothuka sekwenzekile, futhi kuhambelana ngezinga lokuqothuka lokukhumbula (IMilad neQuirk 2002). Ubumbano ngaphakathi kwe-IL-mPFC buye baboniswa futhi ukukhuthaza ukugcinwa kwememori yokuqothula, okuholela ekucindezelweni kokwesaba okunesimo (UHryry noGarcia 2002). Ekugcineni, ama-ejenti akhulisa umsebenzi we-metabolic ku-IL-mPFC (UGonzalez-Lima noBruchey 2004) kanye nokukhuthaza ngokuqondile kukagesi kwe-IL-mPFC (UMilad et al. I-2004; UVidal-Gonzalez et al. I-2006; I-Fig. 2B), zombili zikhuthaza inkulumo yokuqothulwa. Ngokubambisana, le mininingwane iphakamisa ukuthi i-IL-mPFC isebenzise ukwesaba ukuvimbela.

 

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Umfanekiso we-2. 

Ukugqamisa umsebenzi ku-cortex ye-prelimbic kukhulisa ukwesaba nokufuna izidakamizwa, kuyilapho ukuthuthukisa umsebenzi ku-crex ye-infralimbic kunemiphumela emibi. (A) I-microstimulation kagesi (stim) ye-prelimbic (PL) cortex ithuthukisa ukwesaba okunesimo esilingana nokulawula okungafakwanga (cont). Amanani ku y-axis amelela ukwanda kwamaphesenti kuya kwethoni elinezintambo zokuthuthumela. I-Microstimulation yenziwa esimisweni sokuqala sokuqothulwa (UVidal-Gonzalez et al. I-2006). Ngokufuna izidakamizwa, i-PL yasebenza ngokufakwa kwangaphakathi kwe-dopamine (30 nmol / side) ngaphambi kweseshini yokuqothulwa, ngemuva kokuqeqeshwa okubanzi kokuqothula. Ukuqothuka kwesisekelo ukuphendula esimisweni ngaphambi kokuhlolwa kwe-PL kuboniswa njenge-control (cont). Amanani ku y-axis amele imishini yokuxhuma kulayini we-cocaine ngaphambili -UMcFarland noKalivas 2001). (B) I-microstimulation kagesi (stim) ye-infralimbic (IL) cortex inciphisa ukwesaba okunesimo esilingana nokulawula okungafakwanga (cont). Imininingwane eqoqwe ocwaningweni olufanayo (UVidal-Gonzalez et al. I-2006) ekukhuthazeni kwe-PL kuboniswe ku A. Ngokufuna izidakamizwa, i-IL yavuselelwa ukufakwa kwasendaweni kwe-AMPA (0.1 nmol / side) ngaphambi kokuhlolwa kokuqina kwe-cocaine (10 mg / kg, ip), ngemuva kokuqeqeshwa kakhulu. Ukuphinda ufake amandla wokucindezela kwi-cocaine ebhangqiwe ngaphambili kwakusetshenziswa njengesilinganiso sokufuna i-cocaine (y-axis). Amanani wokuphinda akhokhelwe izilwane ezincane ezifakwa emotweni ngaphambi kovivinyo lokuphinda lukhonjiswe njengezilawuli (cont) (UPeter et al. I-2008a). Ukubekwa okumelele kwe-electrode elenzelela amandla noma amathiphu wokufaka inalithi ku-PL (A) kanye ne-IL (B) kukhonjiswa kokubili izivivinyo zokusaba nokufuna izidakamizwa ku kwesokudla yegrafu ngayinye. (*) P <0.05 iqhathaniswa nesimo sokulawula esifanele.

Ubufakazi bamuva nje bukhombisa ukuthi i-prelimbic prefrontal cortex (PL-mPFC) ekhulayo kakhulu ikhulisa ukubonakaliswa kokwesaba (I-Fig. 1). Ngenkathi ama-neurons e-IL-mPFC enyusa umsebenzi kwi-CS lapho ukwesaba kuphansi, ama-neurons we-PL-mPFC akhulisa ukudubula phakathi kokuqothulwa kwangoko, lapho ukwesaba kuphezulu (U-Baeg et al. I-2001; UGilmartin noMcEchron 2005; Laviolette et al. I-2005; I-Burgos-Robles et al. I-2009). Ngaphezu kwalokho, inkambo yesikhathi yezimpendulo ezihanjiswe ngemibiko ye-CS-mPFC neurons ihlangana kakhulu nenkathi yesikhathi yokuqandelwa kwesimo (I-Burgos-Robles et al. I-2009). Ukuqashisa kwe-PL-mPFC kukhulisa ukwesaba okunesimo (UVidal-Gonzalez et al. I-2006; I-Fig. 2A), kanye nokutholakala kwemithi kwe-PL-mPFC kwehlisa ukwesaba (Blum et al. I-2006; ICorcoran neQuirk 2007). Ukugqugquzeleka kwezifunda ezingaphezulu, njenge-dorsal anterior cingrate cortex (ACd-mPFC), akuzange kube nemiphumela ebonakalayo ekwesabeni (UVidal-Gonzalez et al. I-2006); kodwa-ke, ucwaningo lwakamuva lithole ukuthi ukwenziwa kwe-ACd-mPFC kwakukwazi ukunciphisa ukubonakaliswa kokwesaba, kanti nama-neuron we-ACd-mPFC asetshenziswa amandla okusaba (Bissiere et al. I-2008). Lokhu kuphakamisa ukuthi i-ACd-mPFC ingahle ifane ne-PL-mPFC njengesiza esisebenza ukwesaba. Ngakho-ke, kukhona ukwahlukana okusebenzayo kwe-dorsal-ventral ngaphakathi kwe-mPFC okungabhalwa njengomqondo njengokushintsha kwe- “on-off” okulawula inkulumo yesaba (I-Fig. 1).

Imiphumela yokuqala eyengamela ukuvezwa kwesibindi

Ukwehlukaniswa okwehlukanisiwe kwe-mPFC kungalawula ngokwahluka kokwethulwa kwenkulumo ngamatshe okuhlwaya phakathi kwe-amygdala. Ukuqagela okusuka ku-mPFC kuya e-amygdala kukhona glutamatergic, ukuqagela okujabulisayo (Brinley-Reed et al. I-1995). Amaphrojekthi wesifunda we-PL-mPFC ngokuyinhloko aqonde ku-basal amygdala (BA) (I-Vertes 2004; UGabgt et al. I-2005), okubalulekile ekubonakaliseni ukwesaba okunesimo (I-Anglada-Figueroa neQuirk 2005; Herry et al. I-2008). Iziza eziphambili zokugcina imemori yokwesaba e-amygdala yi-amygdala ye-lateral amygdala (LA) (UQuirk et al. I-1995; Repa et al. I-2001), kanye ne-nucleus central (CE) ye-amygdala (UWilensky et al. I-2006; UZimmerman et al. I-2007). Ngoba akukho okuqagelwa okuqondile kusuka ku-LA kuya ku-ukuphuma kwe-neurons yokuphuma, i-LA icatshangwa ukuthi idonsela ukwesaba ukuqagela kwangaphakathi kwe-BA, okubuye kujabulise i-CE (UBlair et al. I-2001). I-PL-mPFC ngaleyo ndlela ijabulisa i-CE, ngendlela efanayo ne-LA, ngokudlulisela okudluliselwe ku-BA (Likhtik et al. I-2005). Ngakho-ke, umphumela ophelele womsebenzi owandayo ku-PL-mPFC uwukhipha umkhiqizo kusukela ku-CE (I-Fig. 3), okudala ukwesaba ngokuqagela ku-hypothalamus kanye ne-brainstem (I-Hopkins neHolstege 1978; LeDoux et al. I-1988).

 

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Umfanekiso we-3. 

Umdwebo wesekethe obonisa ukulawulwa kwangaphambili kokwesaba okunesimo kanye nokuziphatha okufuna i-cocaine. Ukuhlukaniswa okungaphansi kwangaphakathi ne-ventral ye-medial prefrontal cortex (PFC) kukhonjisiwe ku phakathi, kanye nemiphumela yabo eqondile eya ku-amygdala elawula ukwesaba kuboniswe ku kwesokudla, kanye nalabo abaya ku-nucleus accumbens elawula ukufuna kwe-cocaine okukhonjiswe ku- kwesokunxele. Amaphrojekthi we-cortex we-prelimbic (PL) aya kwi-basal (BA) ye-amygdala, ejabulisa indawo ephakathi (CE) ye-amygdala, ngaleyo ndlela ikhuthaza ukuvezwa kokwesaba okunesimo. I-BA futhi ithola okokufaka okujabulisayo okuvela kuma-amygdala e-lateral (LA), okubuye kuqhube ukuvezwa kokwesaba okunesimo. I-crexex ye-infralimbic (IL), ngokugqamile, ijabulisa isigaba se-GABAergic inhibitory neurons eyaziwa ngokuthi yi-cellalated cell (ITC) cell cell. Lama-neurons avimbela i-CE, ngaleyo ndlela avimbele ukwesaba futhi akhuthaze ukuqothulwa. Ngokuqhathanisa, i-PL ne-IL ilawula i-cocaine edinga ukuqagela kwabo okuhlukanisayo kuya ekuhlukaniselweni okuyisiqalo kanye nokuhlukaniswa kwengqimba kwe-nucleus accumbens. Amaphrojekthi we-PL asiza ekuthuthukiseni, okuthuthukisa ukuvezwa kokuziphatha okufuna i-cocaine. Ngokufuna kwe-cocaine ye-cueine, lokhu kungahle kufake phakathi ukuqagela okuphakathi nge-BA ukufinyelela umnyombo (umugqa omncane oluhlaza). I-IL ihlela igobolondo, elikhuthaza ukuvezwa kokuqothuka. Kusazonqunywa ukuthi ukuphuma kulezi zingxenye ezimbili zama-accumbens kuyithinta kanjani ngokuhlukile indlela yokuziphatha kokufuna i-cocaine (bona umbhalo ngemininingwane). Green sibonisa izindlela ezenza kusebenze ukwesaba nokufuna i-cocaine. Okubomvu kubonisa izindlela ezivimbela ukwesaba nokufuna i-cocaine.

I-IL-mPFC futhi ithumela ukubikezela okujabulisayo kuma-amygdala, kepha ngokukhethekile ihlose izindawo eziqukethe ama-GABAergic neurons ekuhlukaniselweni okwalandela kwe-kinus central kanye nama-cell massated (ITCs), abekwe phakathi kwe-basolateral amygdala tata (BLA) ne I-CE (McDonald et al. I-1996; Berretta et al. I-2005; I-Fig. 3). Lawa ma-ITC angaba indawo yokuqothuka kwenkumbulo yokuqothulwa, ngoba akhombisa ukubumbana kwe-NMDA receptor- (I-Royer ne-Pare 2002). Umsebenzi ku-IL-mPFC ungakhuthaza ukuqothulwa ngokubandakanya i-ITC-Mediated feed-phambili inhibition ye-CE.

Ngokuhambisana nale modeli yokulawulwa kwe-amygdala yokubonisa ukwesaba, ubufakazi bamuva nje bukhombisa ukuthi ukuqothuka kungabandakanya ukuhlanganiswa kokuqina okujabulisayo kuma-ITCs kanye nokuncipha kokuphuma okujabulisayo okuvela ku-LA. Ngokuqondile, UJüngling et al. (2008) buthole ubufakazi obusekela ukuthuthukiswa okuyisisekelo kokudluliselwa kwe-glutamatergic kuma-ITCs ngesikhathi sokuqothulwa kokwesaba okunesimo. Ukubandakanyeka kwama-ITCs ekuboniseni inkumbulo yokuqothulwa kuhlolwe ngokuqondile ngabazali nabasebenza nabo, okukhombisile ukuthi izilonda ezikhethiwe zama-ITC zidale ukuthi uvalo lubange ukubuya (Likhtik et al. I-2008). Ngokungeziwe kokuvinjezelwa kokuvinjezelwa, ubufakazi bamuva nje bukhombisa ukuthi ukuqothuka kubandakanya ukucekelwa phansi kwezindlela ezijabulisayo (UKim et al. I-2007). Lababhali bathole ukuthi ukuqothuka kubuyise emuva ukwanda okubangelwa yimo ye-AMPA receptor surface expression e-LA, futhi kuvimba i-AMPA receptor endocytosis ngaphakathi kokuqothuka kwe-LA. Ngokubambisana, le datha iphakamisa ukuthi imiphumela yokuqothula kusuka ekuhlanganisweni kwe-drive athuthukisiwe kuya ezifundeni ze-amygdala ezivimba ukubonakaliswa kokwesaba (i-ITC) futhi kunciphise ukuphuma kusuka ezifundeni eziqhuba inkulumo yesaba (LA), umbono osekelwa ngemodeli yakamuva yokubonisana (Li et al. I-2009).

Ukulawulwa kwangaphambi kokuqothulwa kokufuna izidakamizwa okunesimo

Ngokuziphatha okuphathelene nezidakamizwa, sigxila kwimodeli yokuzilawula ye-cocaine yokubuyela emuva. Kulesi modeli, amagundane afunda ukucindezela i-lever yokulethwa kwe-cocaine ye-intravenous esimweni esithile se-cocaine ngaphezulu kwezinsuku ezimbalwa kuze kube ukuphendula kuzinzile. Lapho i-cocaine ithathelwa indawo nge-saline, ukuqothulwa kokuphendula ku-lever-paired elengiswa esikhathini se-1-2 wk. Ngemuva kokuqothulwa, ukufuna i-cocaine kungabuyiselwa emuva ngokuletha ucwecwe obedwetshwe ngokulethwa kwe-cocaine, imithamo ephansi ye-cocaine uqobo, noma ukucindezela (UDe Wit noStewart 1981; Shaham et al. I-2003; U-Epstein et al. I-2006). Lokhu kubuyiselwa kokudinga izidakamizwa okulandelayo kucatshangwa njengokuphindisela emuva eklinikhi. Ukuvuselela okuvuselela amandla kungenza kusebenze ukufuna i-cocaine ngamasu we-dopaminergic ngaphakathi kwe-PL-mPFC (Ciccocioppo et al. I-2001; UMcFarland noKalivas 2001; McFarland et al. I-2004; I-Fig. 2A). Zombili i-D1 ne-D2 dopamine receptors zifakwe umfutho emandleni we-dopamine yangaphambi kokuqala kokubangela ukubuyela emuva, noma kunjalo ubufakazi buqine ngokwengeziwe kuma-receptors e-D1 (Ciccocioppo et al. I-2001; Ama-capriles et al. I-2003; Sanchez et al. I-2003; ILangeni noRebec 2005). Ngempela, ukuphatha i-cocaine ngqo ku-PL-mPFC kubangela ukubuyela emuva kwe-cocaine (Park et al. I-2002), mhlawumbe ngenxa yokuvinjwa kwendawo kokuthunyelwa kwe-dopamine (Komiskey et al. I-1977).

Ukujikeleza kwe-neural ukubuyela emuva ekufuneni i-cocaine muva nje kubhalwe imephu nge-pharmacologic ekwakheni izifunda zobuchopho be-discrete ngaphambi kokuhlolwa kokubuyiselwa (UMcFarland noKalivas 2001; McFarland et al. I-2004; Bona i-2005). I-PL-mPFC yatholakala njengebucayi ukubuyela emuva kwe-cocaine, ibangelwa izinhlobo eziningi zokuvuselela okuvuselela amandla, kufaka phakathi i-cocaine-paired cices, i-cocaine uqobo, nengcindezi (UMcFarland noKalivas 2001; Ama-capriles et al. I-2003; McLaughlin futhi Bona 2003; McFarland et al. I-2004; UDi Pietro et al. I-2006; kodwa bona UDi Ciano et al. I-2007). Ngakho-ke, ukufakwa kwe-inactivators ye-pharmacological noma ama-dopamine antagonists ku-PL-mPFC kuholela ekunciphiseni ukucindezela kwe-cocaine ngesikhathi sokuhlola kabusha. Muva nje, ukusungulwa kwe-PL-mPFC kuphinde kwatholakala ukuthi kunciphisa ukubuyela emuva kwe-heroin ebangelwa yizo zombili izintambo ezihambisana nama-heroin kanye ne-heroin uqobo (I-LaLumiere neKalivas 2008; Roger et al. I-2008; kodwa bona Schmidt et al. I-2005). Iningi lalezi zifundo liphakamisa ukuthi i-PL-mPFC imele indawo yokugcina ejwayelekile esifundeni sokubuyela emuva kokubili i-cocaine ne-heroin. Ngakho-ke, ngokufana neqhaza le-PL-mPFC ekukhulumeni kokwesaba, i-PL-mPFC nayo isekela ukubonakaliswa kokuziphatha okunesimo sokufuna izidakamizwa (I-Fig. 1).

Ngokubheka indima yayo ehlongozwayo yokuvimbela, ukwenziwa kwe-IL-mPFC kufanele kuphumele ekucindezelweni kwe-cocaine ngemuva kokuqothulwa. Lokhu, noma kunjalo, akubonwanga ezifundweni ezedlule (UMcFarland noKalivas 2001; Ama-capriles et al. I-2003; UFuchs et al. I-2005; UMcLaughlin noFloresco 2007; Koya et al. I-2008). Kunezici ezimbili ezingabangela lokhu. Esokuqala ukuthi i-IL-mPFC ngokuvamile yayingasebenzi ngaphambi kokuphatha ukuvuselela okuvuselela amandla, okuphumela emazingeni aphezulu wokufuna i-cocaine, lapho kuzoba nzima ukwengeziwe ukuthola i-cocaine (okungukuthi, uphahla lwamatshe). Okwesibili ukuthi izintambo ezihlanganisiwe eziboshwe ngokulethwa kwe-cocaine azikaze zicinywe ngaphambi kokuhlolwa kwe-IL-mPFC; Ngakho-ke, ukuqothulwa kwePavlovian kwakungaphelele (Ama-capriles et al. I-2003; Koya et al. I-2008). Uma i-IL-mPFC ingasebenzi ekuqothulweni okulandelayo kokuqothulwa kwe-cocaine noma i-heroin, kukhona ukubuyiselwa okuqinile kokufuna izidakamizwa, okuhambisana nendima evimbelayo yalesi sakhiwo (I-Ovari neLeri 2008; UPeter et al. I-2008a,b). Ngaphezu kwalokho, i-IL-mPFC ekhemisi engaphambi kwamakhemikhali ngaphambi kokuhlolwa kokuphinda ibuye ihlise izinga lokuphinda libuyele (UPeter et al. I-2008a; I-Fig. 2B), iqhubeka futhi i-IL-mPFC ekucindezelweni kokufuna izidakamizwa. Ngokubumbene, ubufakazi obukhona bukhombisa ukuthi i-PL-IL ihlinzeka ngesishintshi sendlela yokubonisa isimo esivumelana nokufuna izidakamizwa, njengoba zenza ukubonisa ukwesaba okunesimo, ikakhulukazi ngemuva kokuqothulwa (Amakhiwane. I-1, 2).

Imiphumela yokuqala eyengamela ukufuna izidakamizwa

Njengoba ukuxhumana okuhlukile kwe-pre-pre-preyaldala-amygdala kuxhumeka kusetshenziselwa i-switch off-off yokwesaba okunesimo, i-anatomy yokuxhuma kokuxhuma okungaphambili (i-prelocal-accumbens) isekela inkinobho yokuvula i-cocaine. I-nucleus accumbens core (core) ithola okokufaka ngokuyinhloko kusuka ku-PL-mPFC, kanti igobolondo le-nucleus accumbens (igobolondo) lithola okokufaka ngokuyinhloko kusuka ku-IL-mPFC (Sesack et al. I-1989; UBrog et al. I-1993; UVoorn et al. I-2004). I-Glutamate ekhishwe ku-PL-mPFC ngaphakathi kokudala okuyisiyingi ibuyisa kokubili i-cocaine ne-heroin (McFarland et al. I-2003, 2004; I-LaLumiere neKalivas 2008; I-Fig. 3) ngokudlulisela okuthethwe nge-AMPA (I-Cornish neKalivas 2000; Park et al. I-2002; I-LaLumiere neKalivas 2008). Ukuqagela kwe-IL-mPFC kugobolondo, ngokuhlukile, kugqugquzela ukuqothulwa kokufuna kwe-cocaine, njengoba ukunqanyulwa kwale ndlela ngemuva kokuqothuka kuphumela ekubuyiseni kwe-cocaine enesimo esifuna ukukhumbula lokho okubonwe ku-IL-mPFC inactivation (UPeter et al. I-2008a). Ngaphezu kwalokho, njengoba ukuqothula kuqhubeka, ukuvela kwegobolondo le GluR1 subunit ye-AMPA receptor kuyanda, kepha ukuveza okuyinhloko akukhona (USutton et al. I-2003). I-Shell expression ye-GluR1 ihlangana kahle nezinga lokuqotelwa kokuziphatha futhi ngokungahambi kahle ngokubuyela emuva kwe-cue-indped (USutton et al. I-2003). Ngakho-ke, i-IL-mPFC ingukufaka okokufaka kwi-glutamatergic kwigobolondo okungenzeka kube nesibopho sokubonisa ukuqothulwa (I-Fig. 3).

Kokubili umnyombo negobolondo kuthumela ukuqagelwa kwe-GABAergic ku-pralidum ye-ventral, elawula ukuphuma kwemoto okudingekayo ekufuneni izidakamizwa (I-Walaas ne-Fonnum 1979; UZahm noHeimer 1990; UHeimer et al. I-1991; Kalivas et al. I-1999). Ama-agaba we-GABA afakwe ku-ventral pallidum anciphisa ukufuna i-cocaine (UMcFarland noKalivas 2001), futhi kwezinye izimo ukuthobeka (UMogenson noNielsen 1983; Izingwegwe neKalivas 1995). Ngakho-ke, kulindeleke ukuthi ukubonwa kwe-GABAergic kusuka kuma-accumbens kuya kwi-pallidum kuzocindezela ukufuna izidakamizwa. Lokhu kuyahambisana nokuvinjezelwa okuphakathi kwemithi kwe-IL-mPFC yokufuna izidakamizwa ngemuva kokuqothulwa, kepha akuhambisani nokusebenziseka okuphakathi kwe-PL-mPFC kokufuna izidakamizwa. Ukwenza kusebenze kokufuna izidakamizwa ngomgogodla kungafaka i-neuropeptide enkephalin. Ama-neuron we-Medium spiny aqhamuka kusuka kumongo kuya kwi-pallidum expression enkephalin (UZahm et al. I-1985), okuthe, uma ikhishwa ngesikhathi sokudubula kaningi, kungavusa ama-all opiod receptors (Waldhoer et al. I-2004) kudala ukuncishiswa kwamazinga we-GABA wasendaweni kanye nokuvinjwa okuncishisiwe ngaphakathi kwe-pallidum (Kalivas et al. I-2001; Schroeder kanye Schneider 2002). Impela, ukuncipha okuncike ku-i opiod ku-Gabe ekhula ngokudingekile kuyadingeka ukuze kubuye i-cocaine (UTang et al. I-2005), umphumela ongaqondiswa ngokukhishwa ngokuhlangana kwe-enkephalin kumugqudu wendlela yokuqongelela (I-Torregrossa et al. I-2008). Ngakho-ke, ukuqagelwa kwe-PL-mPFC ngokusebenzisa umongo kuya ku-pallidum kungasebenza kusebenze ngokufuna izidakamizwa.

Caveats imodeli

Noma imodeli yethu iphakamisa ukunqwabelana kumasekethe wokuqothula ukwesaba nokulutha ngaphakathi kwe-cortex yangaphambi kokuqala kanye nokwehlukana kokunye kokulandela komphumela okuyiwo obhekene nokubonakaliswa kwalezi zinhlobo zalokhu kuziphatha, lokhu kwehluka kungahle kungafani njengoba siphakamisa. Ngaphezu kokuvezwa kokwesaba okunesimo, ama-amygdala nawo angadlala indima ekuvezweni kokufuna izidakamizwa okunesimo. Umsebenzi ku-BA uyingxenye edingekayo yokujikeleza okufunwa izidakamizwa okukhokhisa i-cue (Kantak et al. I-2002; McLaughlin futhi Bona 2003). Lokhu kuqondaniswe ngokwengxenye ngokuxhunyaniswa okubuyisanayo phakathi kwe-PL-mPFC ne-BA, kanye nokuqagelwa okusuka kwi-BA ngqo kuya kumnyombo (UDi Ciano no-Everitt 2004; UFuchs et al. I-2007). Ngakho-ke, okungenani ekufuneni izidakamizwa i-cue-fascinated, kubonakala sengathi kunendathane yendima yokuqagela kusuka ku-PL-mPFC kuya ku-BA ekuqaliseni ukwesaba nokufuna izidakamizwa (I-Fig. 3). Ngokubalulekile, i-CE ye-amygdala futhi ikwazi ukuqalisa ukufuna izidakamizwa, ikakhulukazi ukubuyiselwa okugcizelelwa (U-Erb et al. I-2001; U-Leri et al. I-2002; McFarland et al. I-2004). Ngakho-ke, ukuphuma kwe-CE okuthuthukisiwe kungaba yindlela evamile ekusetshenzisweni kokusaba nokuziphatha okufuna izidakamizwa.

Ngaphezu kwendima yayo ekuvezweni kokuziphatha okufuna izidakamizwa, ama-nucleus accumbens nawo angahileleka ekubonakalweni kokwesaba. Isibonelo, ukwenziwa kwegobolondo kwe-pharmacological kwanele ukuvumela ukugwema kanye nokuziphatha okuvikelayo kokuhlasela kumagundane (UReynolds neBerridge 2001, 2002). Ngenkathi lokhu kusikisela ukuthi okwenzeka egobolondweni kungavimba amandla okubonisa ukwesaba, kukhona futhi ubufakazi obuhlukile, lapho izilonda zegobolondo zinciphise ukubonakaliswa kokwesaba (UJongen-Relo et al. I-2003). Kodwa-ke, izincwadi zixubekile, mhlawumbe ngokwengxenye ingenxa yokungahloniphi okujwayelekile kokuhlukaniswa okuyisisekelo kwegobolondo (IHaralambous neWestbrook 1999; Schwienbacher et al. I-2004; ukuze ubuyekezwe, bheka U-Levita et al. I-2002). Izifundo zesikhathi esizayo ziyadingeka ukuthola ukuthi ama-amygdala nama-accumbens anikezelwe kuphela ukubonakaliswa kokwesaba nokufuna izidakamizwa, ngokulandelana.

Indlela esezingeni eliphakeme yokuqala ye-PTSD kanye nomlutha?

Kunobufakazi obukhulayo obusekela umbono wokuthi i-post-traumatic stress disorder (PTSD) ihlotshaniswa nokwehluleka kokuqothuka. Ocwaningweni lokucabanga kwabantu, omabili ubukhuluUMilad et al. I-2005) nomsebenzi (Phelps et al. I-2004; Kalisch et al. I-2006; UMilad et al. I-2007b) ye-ventral mPFC (vmPFC) ihambelana kahle nokukhumbula okuqothulayo. Iziguli ze-PTSD zikhombisa ukwehla komsebenzi ngaphakathi kwe-vmPFC lapho zivezwa izikhumbuzo ezihlukumezanayo (UBremner et al. I-1999; UShin et al. I-2004; Phan et al. I-2006), kuphakamisa ukuthi i-vmPFC esintwini i-analogous ku-IL-mPFC ku-rodent. Eqinisweni, kusanda kukhonjiswa ukuthi iziguli ze-PTSD azinakukhumbula ukuqothulwa (UMilad et al. I-2008). Ukwehluleka ukwenza kusebenze lezi zifunda kusekela i-hypothesis ebangelwa yi-PTSD ekuhlulekeni kokuqothula ngenxa yokungakwazi ukwenza umsebenzi wokushintsha i-vmPFC off off (I-Fig. 4). Kungenzeka futhi ukuthi i-PTSD ivele kusukela ekusebenzeni ngokweqile ngokushintshana, njengoba ubukhulu kanye nomsebenzi we-dorsal anterior cingulate (dACC) cortex, a Homolog functional of rat PL-mPFC, correlates with expression expression (UMilad et al. I-2007a; I-Fig. 4).

 

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Izindlu zesintu zezindawo eziyindilinga yangaphambili ezilingisa ukwesaba nokulutha. Amachashaza aluhlaza amelela izifunda ze-dACC zabantu ezihlotshaniswe nkulumo yokwesaba, njengoba kuhlolwe yi-fMRI (Phelps et al. I-2004; UMilad et al. I-2007a). Amachashazi aluhlaza okwesibhakabhaka amelela izifunda eziluthweni lwabantu ezihlotshaniswa nokufisa kwe-cocaine ngemuva kokuchayeka ezindabeni ezihlobene ne-cocaine, njengoba kuhlolwa yi-fMRI (IGaravan et al. I-2000) noma imephu ye-PET yokugeleza kwegazi lokubeletha usebenzisa ¹⁵Amanzi afakwe ilebula (Intokazi et al. I-1999). Amachashazi abomvu abonisa izifunda eziseduze ze-vmPFC ezihlobene nokukhumbula ukuqothuka, njengoba kuhlolwe yi-fMRI (Phelps et al. I-2004; Kalisch et al. I-2006; UMilad et al. I-2007b). Icashazi eliphuzi limelela okulingana ne-vmPFC kwezifundo eziluthayo. Lesi sifunda senziwe sasebenza, njengoba kuhlolwe ukwakhiwa kwemephu ye-PET ye-metabolic nge-2-deoxyglucose, ngesikhathi sezindawo ezinxanela i-cocaine, kuphakamisa ukwehluleka ukuqothula (UBonson et al. I-2002). Ngokubambisana, lezi zifundo ziphakamisa ukuthi le vmPFC iyasizakala ngokuxakatha i-IL, kanti izindawo ezise-dacal ze-DACC ziyaziqhenya ngokusebenza kahle kwe-PL. (Isithombe sobuchopho se-MRI siphindwe kabili ngemvume evela kwisoftware yeBrainVoyager Brain Tutor, ngeBrain Innovation BV, Maastricht, Netherlands.)

Ngendlela emangazayo, imilutha yezidakamizwa ibonakala inenkinga yokushintshana okuguqukayo kokufuna izidakamizwa. Ama-cices ahlobene ne-Cocaine asebenzisa i-dACC kwimilutha (UGrant et al. I-1996; Intokazi et al. I-1999; IGaravan et al. I-2000), futhi lokhu kusebenze kuvumelana kahle nezilinganiso ezilingana zokufisa i-cocaine (Intokazi et al. I-1999; I-Fig. 4). Ngakho-ke, lezi "zidakamizwa" kuzindawo zingahle zibe yinkuthazo ku-PL-mPFC ezifundweni ezinkulu zokubuyiselwa kwe-cocaine. Impela, lezi zifunda zi-Homomous Homomous nge-rodent PL-mPFC (I-Ongür ne-Price 2000; UStefanacci no-Amaral 2002). Ukuthi kungenzeka ukuthi lezi “zidakamizwa” ezifundeni zigqagqene nezifunda “zesaba” kuphakanyiswa ukubonwa kokuchayeka kwezigameko ezihlobene nokuhlukumezeka ezigulini ze-PTSD ezinokuxhomekeka komqondo wento ethile kubangela ukufisa kwe-cocaine (UCofiy et al. I-2002).

Ngaphezu kwalokhu kusebenze okuthonywe yi-cocaine ye-dACC, imilutha ikhombisa ukwehla okwenzeka kokudla okwenziwe kuqala ngesikhathi sokuphumula (I-Goldstein no-Volkow 2002). Ucwaningo lwezinkawu lukhombisa ukuthi izifunda ezingena ngaphakathi kwe-cortex yokuqala zingokuqala ukukhombisa ukusilela kokudla emzimbeni ngemuva kokuvezwa kwe-cocaine (UPorrino noLyons 2000; Porrino et al. I-2007). Ngakho-ke, inkinobho yokuqala yokufuna i-cocaine ingahle ithikamezwe ukusetshenziswa kwe-cocaine. Izifundo zesikhathi esizayo ziyadingeka, noma kunjalo, ukuthola ukuthi imilutha yabantu ikhombisa ukwakheka kahle kwangaphambi kokusebenzisa umzimba ngaphambi kokusebenzisa i-cocaine, okungabenza babe sengozini yokusebenzisa kabi izidakamizwa.

Imilutha yabantu ifana neziguli ezinezilonda ze-vmPFC ngezinyathelo ezithile zokulawulwa kokuvinjelwa kokuvinjwa kwengqondo (Bechara 2005). Womabili la maqembu abonakala njengohlobo lokuziphoqelela kokuziphatha okubangelwa ukungakwazi ukuthola izwe elimnandi elivame ukuhlotshaniswa nokwenza izinqumo okuyingozi (Bechara et al. I-1996; UBechara noDamasio 2002). Ngokuthabisako, ukuyekisa ukusebenza kwe-vmPFC kuye kwabonwa kumilutha evezwe ezinqolobaneni ezihlobene ne-cocaine zisebenzisa i-positron emission tomogra (PET) ye-glucose metabolismUBonson et al. I-2002). Le mininingwane iphakamisa ukuthi imilutha ihlushwa yilutho olungafanelekile ku-vmPFC, ibanikeze engcupheni yokuphinde babuye lapho kukhona izinto ezihlobene ne-cocaine. Ngakho-ke, siphakamisa ukuthi umlutha, njengokukhathazeka kokukhathazeka, kungahle kuholele engxenyeni yokwehluleka ukuqothula.

Comorbidity of ukukhathazeka umlutha

Ukusebenzisana phakathi kwamasekethe ngokwesaba umlutha kuyahambisana nokutholakele kokuziphatha. Ukusetshenziswa kwe-cocaine isikhathi eside kuhlangene nemizwa yokukhathazeka, ukwanda okuvela kathathu kuya kane kokuhlaselwa kokwethuka, kanye ne-comorbidity ne-PTSD (I-Cox et al. I-1990; U-Wasserman et al. I-1997; U-O'Brien et al. 2005). Uma izifundo zihlolwa kuqala ukuba khona kokukhathazeka kokukhathazeka, izehlakalo zokusebenzisa i-cocaine ziyakhuphuka, ngisho nangemva kokushintshwa kwezimpawu zomphakathi kanye nokunye ukuphazamiseka kwengqondo (UGoodwin et al. I-2002; USareen et al. I-2006).

I-pathology eyisisekelo ku-cortex yangaphambili ingabeka umuntu engcupheni yokuphazamiseka kokukhathazeka nokuba umlutha. Njengoba kunikezwe ukuthi izilonda ze-vmPFC ziholela ekuziphatheni okukuziphatha kubantu nakubantu bamagundane (Bechara et al. I-1994; UDavidson et al. I-2000; Best et al. I-2002; Chudasama et al. I-2003), ukwehla kwe-vmPFC kwehle kungahle kuholele ku-phenotype enobungozi obukhulu. Ukusekela lokhu, kukhonjisiwe ukuthi iziguli ze-PTSD (Chemtob et al. I-1994; U-Aidman noKollaras-Mitsinikos 2006; UDileo et al. I-2008) nezidakamizwa (UBechara noVander 2005; UVerdejo-Garcia et al. I-2007) zibonakaliswa yi-phenotype engaphoqeleli. Kodwa-ke, izifundo ezinde zokuhlola ukuhlolwa kokuziphatha ngaphambi kokuvezwa kwengozi ziyadingeka ukuthola ukuthi le phenotype ephoqayo ibonakala ngaphambi kokuqala kwe-PTSD.

Ukuhlukumezeka ekusebenzeni kwangaphambi kokuqala kungavela kusuka kokuhlangenwe nakho kwempilo okucindezelayo, kufaka phakathi usizi, ngaleyo ndlela abantu abanqume ukwenza i-PTSD kanye nomlutha (U-Anderson et al. I-2000; U-Weber noReynolds 2004; UHyman et al. I-2007). Kunobufakazi besifo esiveza ukuthi kunokwehla kwesigameko sokuhlukumezeka kwengane esemncane ezigulini ze-PTSD (ICaffo neBelaise 2003). Emalungeni, zombili izingcindezi zempilo yokuqala kanye nengcindezi yobudala kungaholela ekushoneni kokuqothuka kwesaba (Garcia et al. I-2008; Matsumoto et al. I-2008), kungenzeka ngenxa yokuhoxiswa okuphindwe kabili ku-IL-mPFC (Izquierdo et al. I-2006). Ngokufanayo, ukucindezela kwangaphambi kokuphindelela kubangela ukubuyela esimeni zezilwane zokusebenzisa kabi izidakamizwa nakubantu (Shaham et al. I-2000; USinha et al. I-2006).

Imiphumela yokuvezwa kwengcindezi ekusebenzeni kwangaphambili ingasebenzisana nezinto zofuzo ukukhiqiza i-phenotype engabonakali. Isibonelo, ukuba khona kwe-dopamine D2 receptor A1 allele kuhlotshaniswe nokwanda kokuthola i-PTSD (Comings et al. I-1996) kanye nokuhlukumeza i-cocaine (Noble et al. I-1993; Comings et al. I-1994). Ukuba khona kwalokhu kulele kuphumela emazingeni obuchopho ancishisiwe wama-D2 receptors (Noble 2000), okukhumbuza ukusilela kokuqina kwe-dopamine D2 receptor binding egcinwe kumilutha yabantu (Volkow et al. I-2002). Ukuncipha okukhulu kuma-receptor e-striatal D2 kubuye kwaxhunyaniswa nokushoda okuthe xaxa ekuphumuleni imetabolism yangaphambi kwesikhathi kumilutha (Volkow et al. I-1993). Noma kufanele kunqunywe ukuthi ngabe le mikhuba ye-D2 iyimbangela noma umphumela wokulutha, okutholakele kuyahambisana nesichasiselo sofuzo esingenzeka sithuthukise umlutha (Noble et al. I-1997).

Ukwelapha imilutha njengezisulu zokuhlukumezeka

Ama-ejenti akhulisa ukusayina okuqothulayo ku-vmPFC kungaba izindlela zokwelapha eziphumelelayo zokuphazamiseka okuvela ekuhlulekeni kokuqothuka. Kuze kube manje, impumelelo enkulu yomtholampilo iye yatholakala nge-d-cycloserine (DCS), i-agonist engxenye ye-NMDA receptor, enikezwe ngokuhambisana nokwelashwa okuchazayo ekwelapheni ukuphazamiseka kokukhathazeka. I-DCS ikhonjisiwe ukwenza lula ukuqothulwa kwe-acrophobia (URessler et al. I-2004; UDavis et al. I-2006), ukuphazamiseka kokukhathazeka komphakathi (Hofmann et al. I-2006), nokuphazamiseka okucindezelayo okucindezelayo (Kushner et al. I-2007; U-Wilhelm et al. I-2008). Muva nje iDCS isaphenywa njengendlela yokwelapha yokulutha (UBrady et al. I-2008), kepha izifundo kuma-rodents zisekela amandla alo okwenza lula ukuqothulwa kokufuna kwe-cocaine kumodeli yokuthandwayo yendawo evunyelwe yomvuzo wezidakamizwa (Botreau et al. I-2006; UPaolone et al. I-2008). Ngenkathi i-DCS icatshangwa ukuthi isebenze e-amygdala (Ledgerwood et al. I-2003), futhi ingasebenza ku-vmPFC, lapho ukuqiniswa kokuncipha okuncike ku-NMDA kwenzeka (I-Burgos-Robles et al. I-2007; ISotres-Bayon et al. I-2008).

Ngendlela efanayo, umuntu angacabanga ukuphatha abahlukumezekile njengezidakamizwa. Idatha yakamuva iphakamisa ukuthi N-acetylcysteine, i-cysteine ​​prodrug esezingeni eliphakeme, ingahle isebenze ekwelapheni ukuxhomekeka kwe-cocaine (I-LaRowe et al. I-2007). Lesi sidakamizwa kucatshangwa ukuthi sisebenza ngokubuyisela amazinga e-glutamate kuma-accumbens wemilutha esekwe kudatha evela ezifundweni ze-rodent (U-Baker et al. I-2003). Ukuzilawula kwe-cocaine kunciphisa i-glutamate yama-extracellular ngokukhiqiza ukuncipha okungapheli kokushintshana kwe-cystine-glutamate, kanye N-acetylcysteine ​​ibuyisela umsebenzi we-exchanger (U-Baker et al. I-2003; UMadayag et al. I-2007). Ukubuyiselwa kwe-glutamate yangaphandle N-acetylcysteine ​​ivimbela ukuphinda ibuyele kumamodeli wezilwane ngokuvuselela iqembu elilawula ukuphuma kwe-metabotropic glutamate receptors (mGluR2 / 3) (UMoran et al. I-2005). Ngokubalulekile, abakwa-mGluR2 / 3 agonists banciphisa ukukhathazeka kanye nokubuyiselwa kokufuna izidakamizwa kuma-rodents (Schoepp et al. I-2003; Baptista et al. I-2004; UPeter noKalivas 2006),, esekela ukuxhumana okukhona phakathi kokusaba nokubuyela esimeni kabusha. Ngaphezu kwalokho, N-acetylcysteine ​​iyakwazi ukunciphisa izinkanuko ezivezwa yizintambo ezihlobene ne-cocaine ebantwini (I-LaRowe et al. I-2007), kanye nomsebenzi wecala lokufaka i-cueex (I-LaRowe et al. I-2005). Le ndlela "yokubuyisa ubudlova" ingakhulisa ukulahleka kobudlova obangelwa yi-IL-mPFC engasebenzi, ngaleyo ndlela isebenza ukucindezela ukukhathazeka nokufuna izidakamizwa.

Ukuhlola imodeli

Umlutha uqashelwe njengokuphazamiseka kokufunda nememori (I-Kelley 2004; I-Hyman 2005). Kodwa-ke, zimbalwa izifundo eziqhathanise ngokuqondile ukujikeleza kwe-neural okulawula imemori eguquguqukayo, njengaleyo etholwe ngesimo sokusaba sePavlovian, ngenkumbulo yokudla okungenamsoco, njengaleyo etholwe kumamodeli wokuzibusa wokusebenzisa kabi izidakamizwa. Izifundo zesikhathi esizayo kufanele zenzelwe ukuvivinya ubuqiniso bemodeli yokujikeleza esiyicelile (I-Fig. 3) kanye nokuthola ezinye izinto zesifunda, kungaba ngamaphoyinti wokuhlangana noma ukuhlukahluka ngokwesaba umlutha.

Enye indlela engaba lusizo ukuvivinya ukwesaba okunesimo sokuziphatha kanye nesimo sokuziphatha esidinga ukusebenzisa izidakamizwa esilinganisweni esifanayo. UBurke et al. (2006) usebenzise indlela efanayo ukuhlola imiphumela yokuvezwa kwe-cocaine engapheli ekuqothulweni kokwesaba okwenzeka lapho futhi ethola ukuthi amagundane avela ku-cocaine acisha kancane kunokulawula kwe-saline. Abaphenyi baphetha ngokuthi ama-neuroadaptations afakwe yi-cocaine ku-preortal cortex noma izinhloso zayo ezisebenzayo zonakalise ukuvimbela kokuziphatha okwenziwe kuqala. Lesi isithasiselo esijabulisayo esisazophenywa. Isibonelo, i-cocaine yandisa ukubonakaliswa kwe-activator ye-G-protein signaling 3 (AGS3) amaprotheni ku-cortex yangaphambili, futhi kubuyisela lokhu i-neuroadaptation ye-cocaine eyenziwe nge-cocaine kunciphisa ukufuna kwe-cocaine ezivivinyweni ezilandelayo zokubuyela emuva (Bowers et al. I-2004). Kuzoba mnandi uma ukubuyisela emuva lokhu kukhushulwa okubangelwa yi-cocaine okwenziwe ngaphambi kwe-AGS3 expression kwakwanele ukuthuthukisa ukusilela kokuqothuka kwesaba okubonwe UBurke et al. (2006) ukutadisha. Ukuhlolwa okunjalo okungaphakathi kwesifundo kokufuna ukwesaba kanye nezidakamizwa kufanele kuhambisane namasu we-lesion, izifundo ze-c-fos expression, nokuqoshwa kwe-single-unit ukuze kuqhutshekwe nokuhlolisisa ukugcwala kwemijikelezo yokuqothula.

Muva nje, uhlelo lwe-cannabinoid selutholile ukunakwa ngendima yalo ekuqothulweni kwesaba (UMarsicano et al. I-2002; Lin et al. I-2008). Ama-agonists e-CB1 cannabinoid receptor, lapho i-microinfused yaba yi-cortex yangaphambili, yenza kube lula ukuqothuka, kanti abaphikisi be-CB1 basebenzise endaweni yakini ngaphakathi kokuqothulwa kokukhubazeka kwe-cortex (Lin et al. I-2008). Le miphumela ifana naleyo yokuphathwa okuhleliwe kwama-CB1 agents ekuqothulweni kwesaba (UMarsicano et al. I-2002; UChhatwal et al. I-2005; Pamplona et al. I-2006). Ngenkathi imiphumela yabahlinzeki be-CB1 ekuqothulweni kokufuna izidakamizwa ingafundiswanga kahle, imiphumela yabo ekubuyiselweni kokufuna izidakamizwa iyaphikisana nalokho okutholwe ngenhla ekuqothulweni kwesaba. Okusho ukuthi, ama-agonists e-CB1 aphethwe ngokuhlelekile ukubuyiselwa kokudalwa kwe-cocaine ne-heroin, kanti abamelene ne-CB1 bavimbela ukubuyiselwa kokufuna izidakamizwa (UDe Vries et al. I-2001, 2003). Ngokufuna i-heroin, le miphumela iye yenziwa kusisekelo naku-IL-mPFC (I-Alvarez-Jaimes et al. I-2008). Ngakho-ke, le miphumela yabahlinzeki be-CB1 ekufuneni izidakamizwa ekuphikisweni okusobala kwemiphumela yabo ekuqothulweni kwesaba. Izifundo zesikhathi esizayo ziyadingeka ukunquma indlela eyimbangela yalokhu kungafani kwimodeli.

Noma siphakamise ukuthi imiphumela yokuqothulwa, okungenani ngengxenye, ukusuka emsebenzini owandayo ngaphakathi kwesekethe yokuvinjelwa, ukuqothuka kungenzeka futhi ngokuncipha komsebenzi ngaphakathi komjikelezo ojabulisayo. Kunobufakazi bokuthi amasekethe we-inhibitory we-GABAergic ngaphakathi kwe-PL-mPFC asebenza kuseshini yokuqala yokuqothulwa kwe-cocaine (UMiller noMarshall 2004). Lokhu kungasebenzi ku-PL-mPFC kungahle kudingeke ukuvumela ukwenziwa kwe-IL-mPFC ukwenza lula ukufundwa kokuqothuka. I-PL-mPFC kanye ne-IL-mPFC yamagundane, namakhaya okuxhumana anezinkawu nabantu, ayizifunda ezixhumene ngokomzimba (I-Ongür ne-Price 2000; UChiba et al. I-2001; UJones et al. I-2005). Izifundo zesikhathi esizayo ziyadingeka ukuthola ukuthi ukuvimbela kokubuyiselwa kwenzeka yini phakathi kweziteshi zokukhishwa okujabulisayo nezingavimbeleki ze-mPFC, noma ukuthi i-PL-mPFC ne-IL-mPFC bancintisana ngokulawula indlela yokuziphatha. I-Pharmacotherapeutics eshintsha ibhalansi yomsebenzi ekusetshenzisweni kwe-vmPFC kuhlanganiswe nokusebenza kwe-dacC kungaba ngabazohambela phambili ekwelashweni kokukhathazeka nobubi. Mhlawumbe lezi zinyoni ezimbili zokukhathazeka nokulutha zingabulawa ngetshe elilodwa lokuqala.

Ukuvuma

Ucwaningo oluchazwe kulokhu kubukelwa lwalusekelwa izibonelelo ze-NIH i-MH05383 to JP, DA012513 ne-DA005369 kuya ku-PWK, kanye ne-MH058883 ne-MH081975 ku-GJQ

Imibhalo yaphansi

• ↵Umbhali ohambelana ne-3.

  ↵E-mail [i-imeyili ivikelwe]; ifeksi (787) 999-3057.

• I-athikili iku-inthanethi ku- http://www.learnmem.org/cgi/doi/10.1101/lm.1041309.

  • Yamukelwe ngo-Septhemba 30, 2008.
  • Yamukelwe ngoJanuwari 20, 2009.
• I-copyright © 2009 nguCold Spring Harbour Laborator Press

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