Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system

Saki Imai, Takayoshi Mamiya, Akira Tsukada, Yasuyuki Sakai, Akihiro Mouri, Toshitaka Nabeshima, Shizufumi Ebihara

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The tail suspension test (TST) is widely recognized as a useful experimental paradigm for assessing antidepressant activity and depression-like behavior. We have previously identified ubiquitin-specific peptidase 46 (Usp46) as a quantitative trait gene responsible for decreasing immobility time in the TST in mice. This Usp46 mutation has a 3-bp deletion coding for lysine in the open reading frame, and we indicated that Usp46 is implicated in the regulation of the GABAergic system. However, it is not known precisely how the immobile behavior is regulated by the GABAergic system. Therefore, in the present study, we examined whether the immobility time is influenced by drugs affecting the action mediated by GABAA receptor using both 3-bp deleted (the Usp46 mutant) and null Usp46 (Usp46 KO) mice. Nitrazepam, an agonist at the benzodiazepine-binding site of the GABAA receptor, which potentiates the action of GABA, produced a dose-dependent increase in TST immobility time in the Usp46 mutant mice without affecting general behaviors. The Usp46 KO mice exhibited short immobility times comparable to the Usp46 mutant mice, which was also increased by nitrazepam administration. The effects of nitrazepam in the Usp46 mutant and KO mice were antagonized by flumazenil. These results indicate that the 3-bp deleted Usp46 mutation causes a loss-of-function phenotype, and that the GABAA receptor might participate in the regulation of TST immobility time.

Original languageEnglish
Article numbere39084
JournalPloS one
Volume7
Issue number6
DOIs
Publication statusPublished - 14-06-2012

Fingerprint

Hindlimb Suspension
peptidases
ubiquitin
Ubiquitin
Suspensions
Peptide Hydrolases
mice
Nitrazepam
GABA-A Receptors
mutants
receptors
tail suspension test
benzodiazepines
Flumazenil
antidepressants
Mutation
quantitative traits
Benzodiazepines
gamma-Aminobutyric Acid
Antidepressive Agents

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Imai, Saki ; Mamiya, Takayoshi ; Tsukada, Akira ; Sakai, Yasuyuki ; Mouri, Akihiro ; Nabeshima, Toshitaka ; Ebihara, Shizufumi. / Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system. In: PloS one. 2012 ; Vol. 7, No. 6.
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Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system. / Imai, Saki; Mamiya, Takayoshi; Tsukada, Akira; Sakai, Yasuyuki; Mouri, Akihiro; Nabeshima, Toshitaka; Ebihara, Shizufumi.

In: PloS one, Vol. 7, No. 6, e39084, 14.06.2012.

Research output: Contribution to journalArticle

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