Predictors of high ethanol consumption in RIIβ knock-out mice:: Assessment of anxiety and ethanol-induced sedation
Predictors of high ethanol consumption in RIIβ knock-out mice:: Assessment of anxiety and ethanol-induced sedation
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DOI：
10.1097/01.alc.0000141809.53115.71
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发表时间：
2004-10-01
影响因子：
3.2
通讯作者：
Thiele, TE
中科院分区：
文献类型：
--
作者：
Fee, JR;Sparta, DR;Thiele, TE
背景资料：遗传和药理学证据表明，环腺苷酸依赖性蛋白激酶A途径调节神经生物学反应乙醇。缺乏蛋白激酶A的RIIbeta亚基（RIIbeta（-/-））的突变小鼠对乙醇诱导的镇静有抵抗力，并且比同窝野生型小鼠（RIIbeta（+/+））喝更多的乙醇。我们确定了在不同遗传背景下RIIbeta（-/-）小鼠的高乙醇摄入量是否可以通过高基础水平的焦虑或对乙醇镇静作用的抵抗来可靠地预测。两瓶选择程序和一系列行为测试（高架十字迷宫，旷场活动，和零迷宫）用于评估在C57 BL/6 J或129/SvEv × C57 BL/6 J上的RIIbeta（-/-）和RIIbeta（+/+）小鼠中的自愿乙醇消耗和基础焦虑水平。6 J基因背景此外，在腹膜内注射乙醇（3.8g/kg.Results）后，在RIIbeta（-/-）和RIIbeta（+/+）小鼠中测定乙醇诱导的镇静和血液乙醇水平：两种遗传背景的RIIbeta（-/-）小鼠消耗更多的乙醇，并且相对于RIIbeta（+/+）小鼠对乙醇具有更大的偏好。然而，RIIbeta（-/-）小鼠当维持在C57 BL/6 J背景下时显示出降低的基础焦虑水平，但当维持在129/SvEv x C57 BL/6 J背景下时显示出增加的焦虑。与先前的研究一致，RIIbeta（-/-）小鼠对乙醇的镇静作用具有抗性，无论遗传背景如何。最后，RIIbeta（-/-）和RIIbeta（+/+）小鼠表现出相似的血液乙醇levels.Conclusions：这些结果表明，高乙醇消费与耐乙醇的镇静作用，但焦虑的基础水平，以及乙醇代谢，不可靠地预测高乙醇饮用RIIbeta（-/-）小鼠。
Background: Genetic and pharmacological evidence suggests that the cyclic adenosine monophosphate-dependent protein kinase A pathway modulates neurobiological responses to ethanol. Mutant mice lacking the RIIbeta subunit of protein kinase A (RIIbeta(-/-)) are resistant to ethanol-induced sedation and drink significantly more ethanol than littermate wild-type mice (RIIbeta(+/+)). We determined whether high ethanol intake by the RIIbeta(-/-) mice on alternate genetic backgrounds is reliably predicted by high basal levels of anxiety or resistance to the sedative effects of ethanol.Methods: Two-bottle choice procedures and a battery of behavioral tests (elevated plus maze, open-field activity, and zero maze) were used to assess voluntary ethanol consumption and basal levels of anxiety in RIIbeta(-/-) and RIIbeta(+/+) mice on either a C57BL/6J or a 129/SvEv x C57BL/6J genetic background. Additionally, ethanol-induced sedation and blood ethanol levels were determined in RIIbeta(-/-) and RIIbeta(+/+) mice after intraperitoneal injection of ethanol (3.8 g/kg).Results: RIIbeta(-/-) mice on both genetic backgrounds consumed more ethanol and had a greater preference for ethanol relative to RIIbeta(+/+) mice. However, RIIbeta(-/-) mice showed reduced basal levels of anxiety when maintained on the C57BL/6J background but showed increased anxiety when maintained on the 129/SvEv x C57BL/6J background. Consistent with prior research, RIIbeta(-/-) mice were resistant to the sedative effects of ethanol, regardless of the genetic background. Finally, RIIbeta(-/-) and RIIbeta(+/+) mice showed similar blood ethanol levels.Conclusions: These results indicate that high ethanol consumption is associated with resistance to the sedative effects of ethanol but that basal levels of anxiety, as well as ethanol metabolism, do not reliably predict high ethanol drinking by RIIbeta(-/-) mice.