S4A-3 The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC  

作　　者：WANG Wei-sheng JU Yun-yue WANG Yu-jun 刘景根 LIU Jing-gen

机构地区：[1]Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science,Shanghai,201203,China

出　　处：《神经药理学报》2018年第4期65-66,共2页Acta Neuropharmacologica

摘　　要：Aim:Extinction of aversive memories associated with drug withdrawal has been proposed as a therapeutic strategy for the treatment of drug addiction.However,the mechanisms underlying extinction of such memory are poorly understood.This study was,therefore,undertaken to investigate the role of Rho GTPase Rac1-mediated GABAAR endocytosis in the vmPFC in extinction of aversive memories associated with drug withdrawal.Methods:conditioned place aversion(CPA)was used as a model for measurement of the aversive memories of opiate withdrawal.Extinction experiments were performed as described in our previous study(Wang et al.,2012).Results:we found that extinction of CPA required activation of Rac1 in the vmPFC in a brain-derived neurotrophic factor(BDNF)-dependent manner,which triggers actin polymerization via Pak1-cofilin signaling pathway,leading to synaptic localization of activity-regulated cytoskeleton-associated protein(Arc)in the vmPFC.The synaptic Arc further determines GABAA receptor(GABAAR)endocytosis that is necessary and sufficient for vmPFC long-term potentiation and CPA extinction.Thus,extinction of an aversive memory associated with drug withdrawal is intriguingly controlled by Rac1-dependent GABAAR endocytosis in the vmPFC,thereby suggesting therapeutic targets to promote extinction of the unwanted memory.Conclusion:BDNF dependent Rac1 GTPase activation in the vmPFC contributes to aversive memory extinction by Arc-mediated GABAA receptor endocytosis.

关 键 词：conditioned place AVERSION Rho GTPASE RAC1 GABAAR ENDOCYTOSIS EXTINCTION BDNF 

分 类 号：R73[医药卫生—肿瘤]