Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice
Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice
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DOI：
10.1016/j.physbeh.2004.10.007
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发表时间：
2005-01-31
影响因子：
2.9
通讯作者：
Crabbe, JC
中科院分区：
文献类型：
--
作者：
Rhodes, JS;Best, K;Crabbe, JC
由于人类和小鼠之间的内在差异，没有一个单一的小鼠模型可以代表一个复杂的人类特征的所有特征，如酗酒。因此，有必要开发部分模型。一个重要的特征是饮酒到血液乙醇浓度（BEC）达到对生理和/或行为具有可测量影响的水平（>1.0 mg乙醇/ml血液）的程度。目前使用的大多数模型检查相对口服自我管理，从一瓶含有酒精与一个含有水（两瓶偏好饮用），或口服操作性自我管理。在这些程序中，尚不清楚动物何时或是否饮酒至显著水平，因为饮酒是间歇性的，通常发生在24小时内。本研究的目的是确定最佳参数，并评估一个非常简单的程序的可靠性，利用小鼠基因型（C57 BL/6 J），已知饮用大量乙醇。我们在饲养笼中，在黑暗周期的早期，用自来水中含有乙醇的溶液在有限的时间内更换水瓶。小鼠定期饮用足够的乙醇以实现BEC>1.0 mg乙醇/ml血液。提供的乙醇浓度（10%、20%或30%）不影响乙醇消耗量（g/kg体重）。最高的平均BEC值（接近1.6 mg/ml）出现在水-乙醇转换进入暗循环3 h时，并且乙醇供应4 h而不是2 h。乙醇消耗是一致的，在个别小鼠，可靠地预测BEC后，乙醇访问期间。来自三个来源的C57 BL/6 J小鼠提供了相当的数据，而DBA/2 J小鼠在该测试中的饮水量远低于C57 BL/6 J。我们讨论了高通量筛选试验的模型的优点，其目标是找到其他基因型的小鼠过度饮酒，或筛选药物的疗效，在阻止过度饮酒。(C)2004年爱思唯尔公司All rights reserved.
Because of intrinsic differences between humans and mice, no single mouse model can represent all features of a complex human trait such as alcoholism. It is therefore necessary to develop partial models. One important feature is drinking to the point where blood ethanol concentration (BEC) reaches levels that have measurable affects on physiology and/or behavior (>1.0 mg ethanol/ml blood). Most models currently in use examine relative oral self-administration from a bottle containing alcohol versus one containing water (two-bottle preference drinking), or oral operant self-administration. In these procedures, it is not clear when or if the animals drink to pharmacologically significant levels because the drinking is episodic and often occurs over a 24-h period. The aim of this study was to identify the optimal parameters and evaluate the reliability of a very simple procedure, taking advantage of a mouse genotype (C57BL/6J) that is known to drink large quantities of ethanol. We exchanged for the water bottle a solution containing ethanol in tap water for a limited period, early in the dark cycle, in the home cage. Mice regularly drank sufficient ethanol to achieve BEC>1.0 mg ethanol/ml blood. The concentration of ethanol offered (10%, 20% or 30%) did not affect consumption in g ethanol/kg body weight. The highest average BEC (similar to1.6 mg/ml) occurred when the water-to-ethanol switch occurred 3 h into the dark cycle, and when the ethanol was offered for 4 rather than 2 h. Ethanol consumption was consistent within individual mice, and reliably predicted BEC after the period of ethanol access. C57BL/6J mice from three sources provided equivalent data, while DBA/2J mice drank much less than C57BL/6J in this test. We discuss advantages of the model for high-throughput screening assays where the goal is to find other genotypes of mice that drink excessively, or to screen drugs for their efficacy in blocking excessive drinking. (C) 2004 Elsevier Inc. All rights reserved.