Devineni Anita V, McClure Kimberly D, Guarnieri Douglas J, Corl Ammon B, Wolf Fred W, Eddison Mark, Heberlein Ulrike
University of California, San Francisco, San Francisco, CA, USA.
Fly (Austin). 2011 Jul-Sep;5(3):191-9. doi: 10.4161/fly.5.3.16987. Epub 2011 Jul 1.
The relationship between alcohol consumption, sensitivity, and tolerance is an important question that has been addressed in humans and rodent models. Studies have shown that alcohol consumption and risk of abuse may correlate with (1) increased sensitivity to the stimulant effects of alcohol, (2) decreased sensitivity to the depressant effects of alcohol, and (3) increased alcohol tolerance. However, many conflicting results have been observed. To complement these studies, we utilized a different organism and approach to analyze the relationship between ethanol consumption and other ethanol responses. Using a set of 20 Drosophila melanogaster mutants that were isolated for altered ethanol sensitivity, we measured ethanol-induced hyperactivity, ethanol sedation, sedation tolerance, and ethanol consumption preference. Ethanol preference showed a strong positive correlation with ethanol tolerance, consistent with some rodent and human studies, but not with ethanol hyperactivity or sedation. No pairwise correlations were observed between ethanol hyperactivity, sedation, and tolerance. The evolutionary conservation of the relationship between tolerance and ethanol consumption in flies, rodents, and humans indicates that there are fundamental biological mechanisms linking specific ethanol responses.
酒精摄入量、敏感性和耐受性之间的关系是一个重要问题，在人类和啮齿动物模型中都有相关研究。研究表明，酒精摄入量和滥用风险可能与以下因素相关：（1）对酒精兴奋作用的敏感性增加；（2）对酒精抑制作用的敏感性降低；（3）酒精耐受性增加。然而，也观察到了许多相互矛盾的结果。为了补充这些研究，我们采用了不同的生物体和方法来分析乙醇摄入量与其他乙醇反应之间的关系。我们使用了一组20个因乙醇敏感性改变而分离出的黑腹果蝇突变体，测量了乙醇诱导的多动、乙醇镇静、镇静耐受性和乙醇消费偏好。乙醇偏好与乙醇耐受性呈强正相关，这与一些啮齿动物和人类研究结果一致，但与乙醇多动或镇静无关。在乙醇多动、镇静和耐受性之间未观察到成对相关性。果蝇、啮齿动物和人类中耐受性与乙醇消费之间关系的进化保守性表明，存在连接特定乙醇反应的基本生物学机制。
