J Neurosci. 2019 Epreli 4. pii: 3020-17. doi: 10.1523/JNEUROSCI.3020-17.2019.
Benneyworth MA1,2, Ukuva u-MC3, Asp AJ1, Madayag A3, Ingebretson AE1, Schmidt CE1, Silvis KA1, Larson EB1, Ebner SR1, UThomas MJ4.
Abstract
Ukuqonda iinkqubo ze-neurobiological ezikhuthaza ukunqwenela iziyobisi kunye nokuqhuba ukuphinda ubuyele kunakho ukunceda ekujoliseni kwiinzame zokunyanga umlutha. I-nucleus accumbens (NAc) isebenza njenge-substrate ebalulekileyo yomvuzo kunye nokuziphatha okukhuthazwayo, ngokuyinxenye ngenxa yokuguqulwa kwamandla e-synaptic e-excitatory ngaphakathi kwe-cortical-accumbens pathways. Uphononongo lwangoku luphande ikhonkco le-causal phakathi kokubuyiselwa kwe-cocaine-eyenziwe kwindawo ekhethwayo kunye nokuncipha okukhawulezayo kokunyuka okuxhomekeke kwi-cocaine kumandla e-NAc eqokobhe le-synaptic kwiimpuku zamadoda. ICocaine conditioned indawo yokuziphatha ekhethwayo kunye ex vivo I-electrophysiology yeseli epheleleyo ibonise ukuba i-cocaine-primed reinstatement kunye ne-synaptic depotentiation yaphazanyiswa ngokuthintela ukufakwa ngaphakathi kwe-AMPAR nge-intra-NAc iqokobhe le-Tat-GluA2.3Y peptide. Ngaphezu koko, ukubuyisela kwakhona kuqhutywe kukunciphisa okuxhomekeke kwi-mGluR5 kwisignali ye-AMPAR. Ukufakwa kwegobolondo le-Intra-NAc lomchasi we-mGluR5 we-MTEP ivalwe ukubuyiselwa kwe-cocaine-primed kunye nokudityaniswa okuhambelanayo, ngelixa ukufakwa kwe-mGluR5 i-agonist CHPG ngokwayo ikhuthaze ukubuyiselwa kunye namandla e-synaptic adityanisiweyo kwiqokobhe le-NAc. Uvavanyo lwe-Optogenetic lweplastikhi ethe ngqo yesekethe lubonise ukuba inhibition ye-infralimbic cortical input kwiqokobhe le-NAc ivalwe ukubuyiselwa kwe-cocaine-primed, ngelixa uvuselelo oluphantsi lwe-frequency (10 Hz) yale ndlela yokungabikho kwe-cocaine yabangela ukuncipha kwamandla e-synaptic ngokufana noko kubonwayo. nge-cocaine, kwaye yayanele ukukhuthaza ukubuyiselwa ngaphandle komngeni we-cocaine. Ezi datha zixhasa imodeli apho ukunciphisa i-mGluR5-mediated kwi-GluA2-equlathe i-AMPAR kwi-NAc shell synapses efumana igalelo kwi-infralimbic cortex yinto ebalulekileyo ekuqaliseni ukubuyiselwa kwendlela yokuziphatha ye-cocaine-primed.INKCAZO YOKUFUNDAEzi zifundo zichonge ulandelelwano lweziganeko ze-neural apho ukuvezwa kwakhona kwe-cocaine kuvula i-cascade yomqondiso eguqula amandla e-synaptic kwi-nucleus accumbens iqokobhe kwaye ibangele impendulo yokuziphatha eqhutywa yinkumbulo ehambelana neziyobisi.
PMID: 30948476
;