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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Published inJournal of neuroscience research Vol. 85; no. 3; pp. 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 Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.02.2007
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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.
Bibliography:Chinese Academy of Sciences
istex:057B640733589F37DF183A958FFBC2A9B2D9C016
E-Institutes of Shanghai Municipal Education Commission - No. E03003
ArticleID:JNR21148
National Natural Science Foundation of China - No. 30370447
ark:/67375/WNG-RFHF5MBJ-1
Science and Technology Commission of Shanghai Municipality - No. 03DZ14018; No. 03DJ14088
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.21148