Diazepam Accelerates GABA_AR Synaptic Exchange and Alters Intracellular Trafficking.

ABSTRACT: Despite 50+ years of clinical use as anxiolytics, anti-convulsants, and sedative/hypnotic agents, the mechanisms underlying benzodiazepine (BZD) tolerance are poorly understood. BZDs potentiate the actions of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, through positive allosteric modulation of γ2 subunit containing GABA type A receptors (GABA_ARs). Here we define key molecular events impacting γ2 GABA_AR and the inhibitory synapse gephyrin scaffold following initial sustained BZD exposure in vitro and in vivo. Using immunofluorescence and biochemical experiments, we found that cultured cortical neurons treated with the classical BZD, diazepam (DZP), presented no substantial change in surface or synaptic level

SUBMITTER: Lorenz-Guertin JM 

PROVIDER: S-EPMC6497791 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature