Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABAA receptors
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
100
Journal Issue
SUPPL. 2
Pages
14439-14444
Date Issued
2003
Author(s)
Abstract
Neuroactive steroids are potent modulators of γ-aminobutyric acid type A receptors (GABAARs), and their behavioral effects are generally viewed in terms of altered inhibitory synaptic transmission. Here we report that, at concentrations known to occur in vivo, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons that is mediated by extrasynaptic δ subunit-containing GABAARs. The neurosteroid-induced augmentation of this tonic conductance decreases neuronal excitability. Fluctuations in the circulating concentrations of endogenous neuroactive steroids have been implicated in the genesis of premenstrual syndrome, postpartum depression, and other anxiety disorders. Recognition that δ subunit-containing GABAARs responsible for a tonic conductance are a preferential target for neuroactive steroids may lead to novel pharmacological approaches for the treatment of these common conditions.
SDGs
Type
journal article