Ubiquitin-Specific Peptidase 46 (Usp46) Regulates Mouse Immobile Behavior in the Tail Suspension Test through the GABAergic System

Division of Biomodeling, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
PLoS ONE (Impact Factor: 3.23). 06/2012; 7(6):e39084. DOI: 10.1371/journal.pone.0039084
Source: PubMed


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 GABA(A) 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 GABA(A) 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 GABA(A) receptor might participate in the regulation of TST immobility time.

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Available from: Toshitaka Nabeshima, Dec 30, 2014
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    • "The Usp46 KO mice were generated as previously described [2]. The KO mice (17-13906 Usp46 gene trapped mice, TG Resource Bank #6072) were descendants of the mouse strain generated by Trans Genic Inc. (Kumamoto, Japan) using the gene trap technique. "
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