Jury Nicholas J, DiBerto Jeffrey F, Kash Thomas L, Holmes Andrew
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Department of Pharmacology and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alcohol. 2017 Feb;58:53-60. doi: 10.1016/j.alcohol.2016.07.007. Epub 2016 Aug 18.
Rates of alcohol use disorders (AUDs) differ between men and women, and there is also marked variation between sexes in the effects of acute and chronic alcohol. In parallel to observations in humans, prior studies in rodents have described male/female differences across a range of ethanol-related behaviors, including ethanol drinking. Nonetheless, there remain gaps in our knowledge of the role of sex in moderating the effects of ethanol, particularly in models of chronic ethanol exposure. The goal of the current study was to assess various behavioral sequelae of exposing female C57BL/6J mice to chronic intermittent ethanol (CIE) via ethanol vapors. Following four weeks of CIE exposure, adult male and female mice were compared for ethanol drinking in a two-bottle paradigm, for sensitivity to acute ethanol intoxication (via loss of righting reflex [LORR]) and for anxiety-like behaviors in the novelty-suppressed feeding and marble burying assays. Next, adult and adolescent females were tested on two different two-bottle drinking preparations (fixed or escalating ethanol concentration) after CIE. Results showed that males and females exhibited significantly blunted ethanol-induced LORR following CIE, whereas only males showed increased anxiety-like behavior after CIE. Increased ethanol drinking after CIE was also specific to males, but high baseline drinking in females may have occluded detection of a CIE-induced effect. The failure to observe elevated drinking in females in response to CIE was also seen in females exposed to CIE during adolescence, regardless of whether a fixed or escalating ethanol-concentration two-bottle procedure was employed. Collectively, these data add to the literature on sex differences in ethanol-related behaviors and provide a foundation for future studies examining how the neural consequences of CIE might differ between males and females.
酒精使用障碍（AUDs）的发生率在男性和女性之间存在差异，急性和慢性酒精的影响在性别上也有显著差异。与人类的观察结果相似，先前对啮齿动物的研究描述了在一系列与乙醇相关的行为中存在雄性/雌性差异，包括乙醇饮用。尽管如此，我们对性别在调节乙醇作用方面的作用的了解仍然存在差距，特别是在慢性乙醇暴露模型中。本研究的目的是评估通过乙醇蒸气使雌性C57BL/6J小鼠暴露于慢性间歇性乙醇（CIE）后的各种行为后遗症。在CIE暴露四周后，比较成年雄性和雌性小鼠在双瓶范式中的乙醇饮用情况、对急性乙醇中毒的敏感性（通过翻正反射丧失[LORR]）以及在新奇抑制摄食和大理石掩埋试验中的焦虑样行为。接下来，在CIE后对成年和青春期雌性小鼠进行两种不同的双瓶饮用制剂（固定或递增乙醇浓度）测试。结果表明，雄性和雌性在CIE后乙醇诱导的LORR均显著减弱，而只有雄性在CIE后表现出焦虑样行为增加。CIE后乙醇饮用增加也仅在雄性中出现，但雌性的高基线饮用可能掩盖了CIE诱导效应的检测。在青春期暴露于CIE的雌性中，无论采用固定还是递增乙醇浓度的双瓶程序，均未观察到对CIE的饮酒量增加。总体而言，这些数据增加了关于乙醇相关行为性别差异的文献，并为未来研究CIE的神经后果在雄性和雌性之间可能如何不同提供了基础。
