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...
Saved in:
Published in | Journal of neuroscience research Vol. 85; no. 3; pp. 649 - 655 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.02.2007
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
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 |