GABAA-receptor δ subunit knockout mice have multiple defects in behavioral responses to ethanol
GABAA-receptor δ subunit knockout mice have multiple defects in behavioral responses to ethanol
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DOI：
10.1111/j.1530-0277.2001.tb02179.x
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发表时间：
2001-12-01
影响因子：
3.2
通讯作者：
Homanics, GE
中科院分区：
文献类型：
--
作者：
Mihalek, RM;Bowers, BJ;Homanics, GE
背景：γ -氨基丁酸A型受体（gabar）参与介导饮料酒精（乙醇）的一些行为效应。然而，每种受体亚基所赋予的独特药理学和行为反应尚未得到很好的理解。方法：为了解决GABAR δ亚基在介导乙醇反应中的作用，对缺乏该亚基的基因敲除小鼠进行了各种酒精诱导的行为反应测试。结果：我们的研究结果表明，与对照组相比，delta（-/-）缺陷小鼠（delta(-/-)）具有(1)减少的乙醇消耗，(2)减轻慢性乙醇暴露的戒断，以及(3)降低乙醇的抗惊厥（癫痫保护）作用。这些小鼠对乙醇表现出正常的抗焦虑反应，对乙醇表现出正常的低温反应，并产生慢性和急性耐受性。结论：这些结果进一步建立了gabar与乙醇特异性行为反应之间的联系，并开始揭示delta亚基在这些反应中的作用。
Background: The gamma -aminobutyric acid type A receptors (GABARs) are involved in mediating some of the behavioral effects of beverage alcohol (ethanol). However, the unique pharmacological and behavioral responses conferred by each of the various receptor subunits are not well understood,Methods: To address the role of the GABAR delta subunit in mediating ethanol responses, gene knockout mice that lack this subunit were tested for a variety of ethanol-induced behavioral responses.Results: Our results indicate that, compared with controls, delta -deficient mice (delta (-/-)) have (1) reduced ethanol consumption, (2) attenuated withdrawal from chronic ethanol exposure, and (3) reduced anticonvulsant (seizure-protective) effects of ethanol. These mice demonstrate a normal anxiolytic response to ethanol and a normal hypothermic response to ethanol, and they develop both chronic and acute tolerance.Conclusions: These results further establish the link between GABARs and specific behavioral responses to ethanol and begin to reveal the role of the delta subunit in these responses.