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

You Qing Cai, Guo Qiang Cai, Guoxiang Liu, Qing Cai, Jia Hao Shi, Jun Shi, Sun Kai Ma, Xia Sun, Zhe Jin Sheng, Zhen Tong Mei, Dafu Cui, Lihe Guo, Zhugang Wang, Jian Fei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)255-267
Number of pages13
JournalJournal of Neuroscience Research
Volume84
Issue number2
DOIs
StatePublished - Aug 1 2006

Keywords

  • Behavioral
  • Ethanol
  • GABA transporter
  • Knockout
  • Reward

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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