The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABA_A Receptor Endocytosis in the vmPFC.

ABSTRACT: Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA_A receptor (GABA_AR) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA_AR endocytosis and CPA extinction. Knockdown of Rac1 expression within the

SUBMITTER: Wang W 

PROVIDER: S-EPMC6705728 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature