Mice with genetically altered GABA transporter subtype 1 (GAT1) expression show altered behavioral responses to ethanol
Mice with genetically altered GABA transporter subtype 1 (GAT1) expression show altered behavioral responses to ethanol
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DOI：
10.1002/jnr.20884
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Fei, Jian
中科院分区：
文献类型：
--
作者：
Cai, You-Qing;Cai, Guo-Qiang;Fei, Jian
GABA能系统在乙醇的体内作用中起着重要的作用。GABA转运子亚型1（GAT 1）在中枢神经系统中构建高亲和力重摄取位点并调节GABA能传递。在这项研究中，缺乏GAT 1的小鼠是通过同源重组开发的。测试了杂合和纯合GAT 1突变小鼠的乙醇、糖精或奎宁消耗、乙醇条件位置偏好、乙醇条件味觉厌恶、乙醇模拟运动活动和乙醇诱导的镇静/催眠。GAT（-/-）小鼠表现出减少的乙醇厌恶和乙醇奖励，以及对乙醇的镇静/催眠和运动刺激作用的不敏感性，沿着增加的避免奎宁偏好和消费。GAT 1（+/-）小鼠对乙醇和糖精的消耗量显著增加，但乙醇的奖赏和偏好效应增强，对奎宁的回避增加，对乙醇的运动兴奋效应的敏感性增加。这些结果表明，GAT 1，也许在一个双向的方式，调节乙醇的一些行为效应。GAT 1突变小鼠为我们研究乙醇在体内的作用机制提供了一个非常有用的模型。(c)2006威利-利斯公司
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 GAT(-/-) 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. (c) 2006 Wiley-Liss, Inc.