Mechanisms associated with the antidepressant-like effects of L-655,708.

ABSTRACT: Previous research has demonstrated that selective modulation of hippocampal transmission by systemic administration of an α5-GABA_A receptor negative allosteric modulator, L-655,708, reproduces the sustained antidepressant-like (AD-like) effect of R,S-ketamine in the absence of any psychotomimetic or abuse-related effects. Pharmacological, electrophysiological (whole-cell patch clamp), and behavioral approaches were used to examine the mechanisms by which L-655,708 produces plasticity within the hippocampus that accounts for its sustained AD-like effect in rats. Inhibitors of either transcription or translation prevented the sustained AD-like effect of L-655,708. Unlike R,S-ketamine, L-655,708 did not cause an increase in the phosphorylation of the receptor for BDNF, TrkB, in the

SUBMITTER: Bugay V 

PROVIDER: S-EPMC7785005 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature