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 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.
Liu
Guo-Xiang
GX
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Liu
Shuai
S
Cai
Guo-Qiang
GQ
Sheng
Zhe-Jing
ZJ
Cai
You-Qing
YQ
Jiang
Jie
J
Sun
Xia
X
Ma
Sun-Kai
SK
Wang
Long
L
Wang
Zhu-Gang
ZG
Fei
Jian
J
D000374:Aggression / Q000502:physiology*; D000818:Animals; D050485:GABA Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006799:Housing, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D012919:Social Behavior; D013739:Testosterone / Q000097:blood
D050485:GABA Plasma Membrane Transport Proteins; D013739:Testosterone