title: Mice with genetically altered GABA transporter subtype I (GAT1) expression show altered behavioral responses to ethanol.
abstract: 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.
authors: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, Shanghai, China.
authors: You-Qing
authors: YQ
authors: Cai
authors: Guo-Qiang
authors: GQ
authors: Cai
authors: Guo-Xiang
authors: GX
authors: Liu
authors: Qing
authors: Q
authors: Cai
authors: Jia-Hao
authors: JH
authors: Shi
authors: Jun
authors: J
authors: Shi
authors: Sun-Kai
authors: SK
authors: Ma
authors: Xia
authors: X
authors: Sun
authors: Zhe-Jin
authors: ZJ
authors: Sheng
authors: Zhen-Tong
authors: ZT
authors: Mei
authors: Dafu
authors: D
authors: Cui
authors: Lihe
authors: L
authors: Guo
authors: Zhugang
authors: Z
authors: Wang
authors: Jian
authors: J
authors: Fei