GABA Receptors As Targets for Treating Affective and Cognitive Symptoms of Depression

Overview

Journal Trends Pharmacol Sci

Specialty Pharmacology

Date 2023 Aug 5

PMID 37543478

Authors

Bernhard Luscher

Jamie L Maguire

Uwe Rudolph

Etienne Sibille

Affiliations

Soon will be listed here.

Abstract

In the past 20 years, our understanding of the pathophysiology of depression has evolved from a focus on an imbalance of monoaminergic neurotransmitters to a multifactorial picture including an improved understanding of the role of glutamatergic excitatory and GABAergic inhibitory neurotransmission. FDA-approved treatments targeting the glutamatergic [esketamine for major depressive disorder (MDD)] and GABAergic (brexanolone for peripartum depression) systems have become available. This review focuses on the GABA receptor (GABAR) system as a target for novel antidepressants and discusses the mechanisms by which modulation of δ-containing GABARs with neuroactive steroids (NASs) or of α5-containing GABARs results in antidepressant or antidepressant-like actions and discusses clinical data on NASs. Moreover, a potential mechanism by which α5-GABAR-positive allosteric modulators (PAMs) may improve cognitive deficits in depression is presented.

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