Antidepressant-like properties of α2-containing GABAA receptors

Vollenweider, Isabel; Smith, Kiersten S.; Keist, Ruth; Rudolph, Uwe

doi:10.1016/j.bbr.2010.10.009

Cited by 96Neuroscience and Neuropharmacology ResearchTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

Antidepressant-like properties of α2-containing GABAA receptors

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Vollenweider, Isabel, Smith, Kiersten S., Keist, Ruth, Rudolph, Uwe·2011·Behavioural Brain Research

DOI 10.1016/j.bbr.2010.10.009PMC PMC3023881

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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.

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From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [9]
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From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [9]

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Authors: Vollenweider, I., Smith, K. S., Keist, R., & Rudolph, U.
Affiliations: Harvard University (US)
University of Zurich (CH)
Corresponding author: Smith, Kiersten S.
ORCID: Rudolph, Uwe
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2011-02
Volume: 217
Issue: 1
Pages: 77-80
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2010.10.009
PMC: PMC3023881
OpenAlex: W2024324079
Cited by: 96
References: 27
Citations by year: 2026: 6 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 8
FWCI: 2.84
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: GABAergic system, depression, antidepressant-like effects, novelty-suppressed feeding, forced swim test, tail suspension test, sex differences, limbic system, antidepressant targets
MeSH terms: Animals, Depression, Disease Models, Animal, Feeding Behavior, Female, Male, Receptors, GABA-A, Sex Characteristics, Swimming, Mice, Knockout, Hindlimb Suspension, Immobility Response, Tonic, Mice, Mice, 129 Strain

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Antidepressant-like properties of α2-containing GABAA receptors

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