Brexanolone, a neurosteroid antidepressant, vindicates the GABAergic deficit hypothesis of depression and may foster resilience [version 1; peer review: 4 approved]

The GABAergic deficit hypothesis of depression states that a deficit of GABAergic transmission in defined neural circuits is causal for depression. Conversely, an enhancement of GABA transmission, including that triggered by selective serotonin reuptake inhibitors or ketamine, has antidepressant eff...

Full description

Saved in:
Bibliographic Details
Published in:F1000 research 2019, Vol.8, p.751
Main Authors: Lüscher, Bernhard, Möhler, Hanns
Format: Article
Language:English
Subjects:
Antidepressants
Anxiety
Behavior
Binding sites
Central nervous system
Defects
Granule cells
Hypotheses
Intravenous administration
Ketamine
Ligands
Mental depression
Mood
Neural networks
Neurogenesis
Postpartum
Pregnanolone
Review
Serotonin uptake inhibitors
Stress
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The GABAergic deficit hypothesis of depression states that a deficit of GABAergic transmission in defined neural circuits is causal for depression. Conversely, an enhancement of GABA transmission, including that triggered by selective serotonin reuptake inhibitors or ketamine, has antidepressant effects. Brexanolone, an intravenous formulation of the endogenous neurosteroid allopregnanolone, showed clinically significant antidepressant activity in postpartum depression. By allosterically enhancing GABA A receptor function, the antidepressant activity of allopregnanolone is attributed to an increase in GABAergic inhibition. In addition, allopregnanolone may stabilize normal mood by decreasing the activity of stress-responsive dentate granule cells and thereby sustain resilience behavior. Therefore, allopregnanolone may augment and extend its antidepressant activity by fostering resilience. The recent structural resolution of the neurosteroid binding domain of GABA A receptors will expedite the development of more selective ligands as a potential new class of central nervous system drugs.
ISSN:2046-1402
2046-1402
DOI:10.12688/f1000research.18758.1