The immediate and maintained effects of neurosteroids on GABAA receptors

D. Belelli, J. A. Peters, G. D. Phillips, J. J. Lambert (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)
84 Downloads (Pure)

Abstract

Allopregnanolone is an endogenous neurosteroid that acts in a rapid non-genomic manner to enhance the function of the GABAA receptor (GABAAR), the major inhibitory receptor in the mammalian central nervous system (CNS). Consequently, allopregnanolone elicits anxiolytic, antidepressant, anticonvulsant, analgesic and sedative effects. Endogenous allopregnanolone influences neural inhibition and behaviour, with perturbed neurosteroid levels implicated in depressive disorders. The approval of brexanolone (an allopregnanolone formulation) to treat postpartum depression (PPD) has encouraged optimism that they may provide a new approach to treat mood disorders. Elucidating how neurosteroids are distinguished from established GABAAR-active drugs, e.g. benzodiazepines, may improve understanding of depressive disorders and aid drug development for psychiatric conditions. Here, we focus on research highlighting: (1) the acute interaction of neurosteroids with GABAARs incorporating the δ subunit (δ-GABAAR) and (2) how neurosteroids may additionally act on a slower time scale to enhance expression of δ-GABAARs, thereby providing sustained therapeutic benefit.

Original languageEnglish
Article number100333
Pages (from-to)1-9
Number of pages9
JournalCurrent Opinion in Endocrine and Metabolic Research
Volume24
Early online date20 Feb 2022
DOIs
Publication statusPublished - Jun 2022

Keywords

  • Allopregnanolone
  • Brexanolone
  • GABA receptors
  • Major depressive disorder
  • Neurosteroids
  • Postpartum depression

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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