Reduced aggression in mice lacking GABA transporter subtype 1

Guoxiang Liu, Shuai Liu, Guo Qiang Cai, Zhe Jing Sheng, You Qing Cai, Jie Jiang, Xia Sun, Sun Kai Ma, Long Wang, Zhu Gang Wang, Jian Fei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Dysregulation of the brain GABAergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central GABAergic activity, dysfunction of the GABA transporter subtype 1 (GAT1) represents a potential mechanism mediating pathologic aggression. We provide evidence that GAT1-/- mice and GAT1+/- mice exhibit lower aggressive behavior both in home cage resident-intruder test and neutral arena resident-intruder test, compared to wild-type mice (GAT1+/+). The pharmacologic effects of the GAT1 inhibitor, tiagabine and the GABA A receptor antagonist, bicuculline have been assessed in GAT1+/+ mice: tiagabine inhibits attacks but bicuculline induces attacks. Compared to GAT1+/- and +/+ mice, the GAT1-/- mice displayed a normal circadian pattern of home cage activity, but more activity overall. Meanwhile, reduced testosterone concentration was found in GAT1-/- mice compared to GAT1+/+ mice but not in GAT1+/+ mice treated with tiagabine, suggesting that testosterone is not directly involved in GAT1 mediated aggressive behavior regulation. These results showed that GAT1 is an important target involved in the regulation of aggressive behavior in mice, and long-term dysfunction of GAT1 may also result in the alteration of testosterone secretion.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalJournal of Neuroscience Research
Volume85
Issue number3
DOIs
StatePublished - Feb 15 2007

Keywords

  • Aggression
  • GABA
  • GABA transporter
  • Gene knock out mouse

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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