Mice with genetically altered GABA transporter subtype I (GAT1) expression show altered behavioral responses to ethanol.
It is widely accepted that the GABAergic system plays an important role in the action of ethanol in vivo. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites in the CNS and regulates GABAergic transmissions. In this study, mice lacking the GAT1 were developed by homologous recombination. Both hetero- and homozygous GAT1 mutant mice were tested for ethanol, saccharin or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and ethanol-induced sedation/hypnosis. The GAT1(-/-) mice showed decreased ethanol aversion and ethanol reward, and insensitivity to both the sedative/hypnotic and the motor stimulant effects of ethanol, along with increased avoidance of quinine preference and consumption. GAT1(+/-) mice showed significantly increased consumption of ethanol and saccharin, however, enhanced the rewarding and preference effect of ethanol, increased avoidance of quinine, and higher sensitivity to the motor stimulant effect of ethanol. These results demonstrate that GAT1, perhaps in a bi-directional way, modulates some behavioral effects of ethanol. The GAT1 mutant mice provided us a very useful model to investigate the mechanisms of ethanol action in vivo.
Cai
You-Qing
YQ
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, Shanghai, China.
Cai
Guo-Qiang
GQ
Liu
Guo-Xiang
GX
Cai
Qing
Q
Shi
Jia-Hao
JH
Shi
Jun
J
Ma
Sun-Kai
SK
Sun
Xia
X
Sheng
Zhe-Jin
ZJ
Mei
Zhen-Tong
ZT
Cui
Dafu
D
Guo
Lihe
L
Wang
Zhugang
Z
Fei
Jian
J