Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.
Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.
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DOI：
10.1016/j.alcohol.2015.02.003
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
De Biasi M
中科院分区：
文献类型：
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作者：
Perez EE;De Biasi M
酒精是世界上最普遍的成瘾物质之一。戒断症状是由习惯性饮酒者突然停止饮酒引起的。情感和身体症状的出现产生了一种促进复发的状态。小鼠提供了一种临床前模型，可用于研究酒精依赖和戒断，同时控制遗传和环境变量。使用液体乙醇饮食提供了一种可靠的方法，用于诱导酒精依赖的小鼠，但这种方法是不切实际的进行高通量药理学筛选时，或比较多个品系的基因工程小鼠。本研究的目的是比较长期接受液体乙醇饮食治疗的小鼠与接受短期乙醇治疗的小鼠的戒断相关行为，短期乙醇治疗包括每日注射含有乙醇脱氢酶抑制剂4-甲基吡唑的乙醇。乙醇处理后24小时，在开放场地竞技场、高架十字迷宫、大理石掩埋试验中对小鼠进行试验，或在自发乙醇戒断期间对小鼠的躯体体征变化进行试验。无论乙醇给药途径如何，在戒断小鼠中，强迫样和强迫样行为以及体征均显著升高。因此，短期乙醇治疗可用作筛选工具，用于在投资于更耗时的乙醇治疗之前测试遗传和药理学试剂。
Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behavior, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time consuming ethanol treatment.