GABAB Receptors: Anxiety and Mood Disorders

Curr Top Behav Neurosci. 2022:52:241-265. doi: 10.1007/7854_2020_171.

Abstract

Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, acts at the ionotropic GABAA and GABAC receptors, and the metabotropic GABAB receptor. This chapter summarizes the studies that have investigated the role of the GABAB receptor in stress-related psychiatric disorders including anxiety and mood disorders. Overall, clinical and preclinical evidences strongly suggest that the GABAB receptor is a therapeutic candidate for depression and anxiety disorders. However, the clinical development of GABAB receptor-based drugs to treat these disorders has been hampered by their potential side-effects, particularly those of agonists. Nevertheless, the discovery of novel GABAB receptor allosteric modulators, and increasing understanding of the influence of specific intracellular GABAB receptor-associated proteins on GABAB receptor activity, may now pave the way towards GABAB receptor therapeutics in the treatment of mood and anxiety disorders.

Keywords: Anxiety; Depression; GABAB receptor; Hippocampal neurogenesis; Mood; Stress; Stress resilience.

MeSH terms

  • Anxiety / drug therapy
  • Anxiety Disorders / drug therapy
  • Humans
  • Mood Disorders* / drug therapy
  • Receptors, GABA*
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid

Substances

  • Receptors, GABA
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid