...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Addiction biology >Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadol.
【24h】

Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadol.

机译：缺乏Gad2的小鼠表现出乙醇，氟西epa和加巴沙多的行为改变。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gamma-aminobutyric acid (GABA) is synthesized in brain by two isoforms of glutamic acid decarboxylase (Gad), Gad1 and Gad2. Gad1 provides most of the GABA in brain, but Gad2 can be rapidly activated in times of high GABA demand. Mice lacking Gad2 are viable whereas deletion of Gad1 is lethal. We produced null mutant mice for Gad2 on three different genetic backgrounds: predominantly C57BL/6J and one or two generations of backcrossing to 129S1/SvimJ (129N1, 129N2). We used these mice to determine if actions of alcohol are regulated by synthesis of GABA from this isoform. We also studied behavioral responses to a benzodiazepine (flurazepam) and a GABAA receptor agonist (gabaxadol). Deletion of Gad2 increased ethanol palatability and intake and slightly reduced the severity of ethanol-induced withdrawal, but these effects depended strongly on genetic background. Mutant mice on the 129N2 background showed the above three ethanol behavioral phenotypes, but the C57BL/6J inbred background did not show any of these phenotypes. Effects on ethanol consumption also depended on the test as the mutation did not alter consumption in limited access models. Deletion of Gad2 reduced the effect of flurazepam on motor incoordination and increased the effect of extrasynaptic GABAA receptor agonist gabaxadol without changing the duration of loss of righting reflex produced by these drugs. These results are consistent with earlier proposals that deletion of Gad2 (on 129N2 background) reduces synaptic GABA but also suggest changes in extrasynaptic receptor function.
机译：γ-氨基丁酸（GABA）是由谷氨酸脱羧酶（Gad）的两种同工型Gad1和Gad2在大脑中合成的。 Gad1提供了大脑中的大部分GABA，但在GABA需求量很高的时候，Gad2可以被迅速激活。缺乏Gad2的小鼠是可行的，而Gad1的缺失是致命的。我们在三种不同的遗传背景下生产了针对Gad2的无效突变小鼠：主要为C57BL / 6J和与129S1 / SvimJ（129N1、129N2）回交的一两代。我们使用这些小鼠来确定酒精的作用是否受该同工型合成GABA的调控。我们还研究了对苯二氮卓类药物（氟拉西m）和GABAA受体激动剂（加巴沙朵）的行为反应。删除Gad2可以增加乙醇的适口性和摄入量，并稍微降低乙醇诱导的戒断的严重性，但是这些作用在很大程度上取决于遗传背景。 129N2背景突变的小鼠表现出上述三种乙醇行为表型，但C57BL / 6J近交背景没有显示任何这些表型。对乙醇消耗的影响还取决于测试，因为该突变不会改变有限访问模型中的消耗。删除Gad2可减少氟西epa对运动不协调的影响，并增强突触外GABAA受体激动剂加巴沙朵的作用，而不会改变这些药物产生的扶正反射丧失的持续时间。这些结果与先前的建议一致，即删除Gad2（在129N2背景下）会降低突触GABA，但也暗示突触外受体功能的改变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号