Reduced aggression in mice lacking GABA transporter subtype 1

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 evide...

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Bibliographic Details
Published in:Journal of neuroscience research 2007-02, Vol.85 (3), p.649-655
Main Authors: Liu, Guo-Xiang, Liu, Shuai, Cai, Guo-Qiang, Sheng, Zhe-Jing, Cai, You-Qing, Jiang, Jie, Sun, Xia, Ma, Sun-Kai, Wang, Long, Wang, Zhu-Gang, Fei, Jian
Format: Article
Language:English
Subjects:
aggression
Aggression - physiology
Animals
GABA
GABA Plasma Membrane Transport Proteins - deficiency
GABA Plasma Membrane Transport Proteins - genetics
GABA Plasma Membrane Transport Proteins - physiology
GABA transporter
gene knock out mouse
Housing, Animal
Male
Mice
Mice, Knockout
Motor Activity - physiology
Social Behavior
Testosterone - blood
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Summary: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 GABAA 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. © 2006 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.21148