Antidepressant-like properties of α2-containing GABA(A) receptors.
Behav Brain Res
; 217(1): 77-80, 2011 Feb 02.
Article
em En
| MEDLINE
| ID: mdl-20965216
ABSTRACT
Growing evidence suggests that altered function of the GABAergic system can contribute to the pathophysiology of depression. Many GABAergic effects are mediated via ionotropic GABA(A) receptors, which are functionally defined by their α subunit (α1-α6). Although it remains unknown which specific GABA(A) receptor population mediates depressive-like effects, we posit that α2-containing GABA(A) receptors, which are highly expressed in limbic regions, may underlie these behaviors. We hypothesized that genetic inactivation of α2-containing GABA(A) receptors would generate a depressive-like phenotype in mice. Male and female wild type, α2 heterozygous, and α2 homozygous knockout mice generated on the 129X1/SvJ background were examined in the novelty-suppressed feeding (NSF) test, the forced swim test (FST) and the tail suspension test (TST). Male α2 knockout mice took longer to eat in the NSF test and became immobile faster and remained immobile longer when challenged in the FST and the TST compared to wild types. In females significant genotypic differences were only observed in the FST. We conclude that GABAergic inhibition acting via α2-containing GABA(A) receptors has an antidepressant-like effect in vivo and that these receptors represent a specific molecular substrate that can regulate depressive-like states. α2-containing GABA(A) receptors may therefore represent a novel target for the development of more effective antidepressants.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de GABA-A
/
Depressão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos