The immediate and maintained effects of neurosteroids on GABAA receptors. (June 2022)

• Record Type: Journal Article
• Authors: Belelli, D.; Peters, J.A.; Phillips, G.D.; Lambert, J.J.
• Is Part Of: Current opinion in endocrine and metabolic research. Volume 24(2022)
• Publication Date: 2022-06
• Subjects: GABAA receptors -- Neurosteroids -- Allopregnanolone -- Brexanolone -- Postpartum depression -- Major depressive disorder; Endocrine glands -- Diseases -- Periodicals; Metabolism -- Disorders -- Periodicals; Endocrine System Diseases; Metabolic Diseases; Endocrine glands -- Diseases; Metabolism -- Disorders; Periodical; Electronic journals; Periodicals; Electronic journals; 616.4
• DOI: 10.1016/j.coemr.2022.100333
• Languages: English
• ISSNs: 2451-9650

Abstract

Abstract: Allopregnanolone is an endogenous neurosteroid that acts in a rapid non-genomic manner to enhance the function of the GABAA receptor (GABAA R), 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 GABAA R-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 GABAA Rs incorporating the δ subunit (δ-GABAA R) and (2) how neurosteroids may additionally act on a slower time scale to enhance expression of δ-GABAA Rs, thereby providing sustained therapeutic benefit.