Mice with genetically altered GABA transporter subtype I (GAT1) expression show altered behavioral responses to ethanol

• Published in: Journal of neuroscience research Vol. 84; no. 2; pp. 255 - 267
• Main Authors: Cai, You-Qing, Cai, Guo-Qiang, Liu, Guo-Xiang, Cai, Qing, Shi, Jia-Hao, Shi, Jun, Ma, Sun-Kai, Sun, Xia, Sheng, Zhe-Jin, Mei, Zhen-Tong, Cui, Dafu, Guo, Lihe, Wang, Zhugang, Fei, Jian
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2006
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Behavior, Animal - drug effects; behavioral; Blotting, Northern; Blotting, Southern; Brain - drug effects; Brain - metabolism; Central Nervous System Depressants - metabolism; Central Nervous System Depressants - pharmacology; Conditioning, Classical - drug effects; ethanol; Ethanol - metabolism; Ethanol - pharmacology; GABA Plasma Membrane Transport Proteins - biosynthesis; GABA Plasma Membrane Transport Proteins - genetics; GABA transporter; knockout; Mice; Mice, Knockout; Quinine - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; reward; Saccharin - pharmacology; Sweetening Agents - pharmacology; Synaptosomes - drug effects; Synaptosomes - physiology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20884

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. © 2006 Wiley‐Liss, Inc.