J Neurosci. 2016 Sep 21;36(38):9949-61. doi: 10.1523/JNEUROSCI.0937-16.2016.
I-Beloate LN1, Omrani A2, Adan RA2, I-Webb IC3, Coolen LM4.
abstract
Ukuhlangenwe nakho kokuziphatha kobulili kubangela ukujeziswa komvuzo we-amphetamine, umphumela oncike esikhathini sokuvinjwa komvuzo wokuya ocansini. Ngaphambilini sakhombisa ukuthi i-ΔFosB ku-nucleus accumbens (NAc) ingumlamuli osemqoka walokhu kuqonda kwesiphambano, ngokunokwenzeka nge-dopamine receptor activation. Kodwa-ke, indima ye-mesolimbic dopamine yokuziphatha kokuya ocansini noma ukuzwela esiphambanweni phakathi komvuzo wemvelo nowezidakamizwa ayaziwa. Lokhu kwahlolwa kusetshenziswa ama-receptor e-inhibitory designer receptors enzelwe kuphela izidakamizwa zomklami endaweni yama-dopamine cell e-ventral tegmental area (VTA). I-rAAV5 / hSvn-DIO-hm4D-mCherry yafakwa kwi-VTA ye-TH: Amagundane amadala abantu besilisa. Abesilisa bathole i-clozapine N-oxide (CNO) noma imijovo yemoto ngaphambi kwezinsuku zokulandelana noma zokuphathwa kwe-5. Ngemuva kwenkathi yokuvinjwa kwe-7 d, abesilisa bahlolwe ukuthi bakhethwe kanjani endaweni ye-amphetamine. Okulandelayo, abesilisa bajovwa nge-CNO noma imoto ngaphambi kokuzalela noma ukuphathwa ngokuhlaziywa kwe-cFos yokuluthwa kokutholwa, isipiliyoni sezocansi esiqhutshwa ΔFosB, kanye nokwehliswa kwesayizi we-VTA dopamine soma. Imiphumela iveze ukuthi i-CNO ayithintekanga ekuziphatheni kokuguga. Esikhundleni salokho, i-CNO ivikele umuzwa wezocansi-obangela i-cross-sensitization ye-amphetamine CPP, i-andFosB ku-NAc kanye ne-medial prefrontal cortex, futhi iyancipha ngosayizi we-VTA dopamine soma. Ukuchazwa kwe-hm4D-mCherry bekucacile kumaseli we-VTA dopamine futhi i-CNO ivinjiwe ukucashunwa kanye nencazelo ye-cFos ye-mating engene kumaseli we-VTA dopamine. Lokhu okutholakele kunikeza ubufakazi obuqondile bokuthi i-VTA dopamine activation ayidingeki ekuqaleni noma ukusebenza kokuziphatha kocansi. Esikhundleni salokho, i-VTA dopamine inomthelela ngqo ekwandeni kokungazweli kokusetshenziswa kwezidakamizwa kulandela ukulahleka komvuzo wemvelo ngokubangela i-neuroplasticity emgodini we-mesolimbic ngesikhathi sesipiliyoni somvuzo wemvelo.
ISITATIMENDE SESITOLO:
Izidakamizwa zokuhlukunyezwa zisebenza ezindleleni ze-neural ezihlanganisa ukufundiswa kwemvelo nokuvuza. Ukuvezwa kwemikhuba yokuziphatha yemvelo kungashintsha umvuzo ohlobene ngokulandela izidakamizwa. Ngokuqondile, isipiliyoni ngokuziphatha ngokobulili, kulandelwa isikhathi sokuzigwema ekuziphatheni ngokocansi, kubangele ukukhuphula umvuzo we-amphetamine kumagundane angamadoda. Lolu cwaningo lubonisa ukuthi ukuvuselelwa kwe-ventral tegmental area dopamine neurons ngenkathi isipiliyoni socansi ilawula ukukhuthazwa kokunciphisa umvuzo we-amphetamine. Okokugcina, ukuvuselelwa kwe-ventral tegmental cell activation cell kubalulekile ekuvumelaneni kwe-neural-induced neuralus accumbens, prefrontal cortex, kanye nendawo ye-ventral tegmental. Lokhu kutholakala kubonisa indima ye-mesolimbic dopamine ekusebenzisaneni phakathi kwemivuzo yemvelo kanye nezidakamizwa, futhi ukukhomba i-mesolimbic dopamine njengomlamuleli oyinhloko wezinguquko ekungcupheni kokusetshenziswa kwezidakamizwa ngemuva kokulahlekelwa umvuzo wemvelo.
Amagama angukhiye: FosB; mesolimbic; ama-nucleus accumbens; i-prefrontal cortex; i-psychostimulant; umvuzo
I-PMID: 27656032
I-DOI: 10.1523 / JNEUROSCI.0937-16.2016
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