Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.
Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, Illinois.
Alcohol Clin Exp Res. 2018 Feb;42(2):286-294. doi: 10.1111/acer.13571. Epub 2018 Jan 8.
Recently, the incidence of binge drinking by women has increased. Binge drinking is detrimental to women's health, yet the biological mechanisms that promote excessive drinking by women are not well understood. One method of assessing binge-like ethanol (EtOH) consumption in mice is the drinking in the dark (DID) test, in which mice drink sufficient EtOH to achieve intoxication. In this study, we directly compared male, female, and ovariectomized (OVX) mice for DID and tested whether 17β-estradiol (E2) contributes to DID. We also measured whether DID varies throughout the estrous cycle and whether repeated intermittent DID impacts the estrous cycle.
Male, female, and OVX C57BL/6J mice were tested for DID for 2 hours per day on days 1 to 3 and for 4 hours on day 4 using a single bottle containing 20% EtOH. To measure the effects of E2 on DID, OVX mice were treated with estradiol benzoate (EB) or vehicle daily starting 2 weeks prior to the drinking test and throughout the DID procedure. In a separate group of experiments, EtOH consumption and estrous cycle phase were measured in freely cycling mice that were drinking EtOH or water 5 days per week for 2 or 6 weeks.
Female mice consumed more EtOH than male and OVX mice. Treatment with EB increased EtOH consumption by OVX mice compared with vehicle-treated controls. However, EtOH intake did not vary across the estrous cycle, nor did long-term DID alter the estrous cycle.
These results demonstrate that ovarian hormones, specifically E2, contribute to increased EtOH consumption by female mice in the DID test. Although ovarian hormones contribute to this behavior, EtOH consumption is not affected by estrous cycle phase in freely cycling mice. This study provides a framework for understanding the factors that contribute to binge drinking in females.
最近,女性 binge drinking 的发生率有所增加。Binge drinking 对女性健康有害,但促进女性过度饮酒的生物学机制尚不清楚。一种评估小鼠 binge-like 乙醇(EtOH)消耗的方法是暗饮(DID)测试,其中小鼠饮用足够的 EtOH 以达到醉酒状态。在这项研究中,我们直接比较了雄性、雌性和去卵巢(OVX)小鼠的 DID,并测试了 17β-雌二醇(E2)是否有助于 DID。我们还测量了 DID 是否在整个发情周期中变化,以及重复间歇性 DID 是否会影响发情周期。
雄性、雌性和 OVX C57BL/6J 小鼠在第 1 至 3 天每天进行 2 小时 DID 测试,在第 4 天进行 4 小时 DID 测试,使用含有 20% EtOH 的单个瓶子。为了测量 E2 对 DID 的影响,OVX 小鼠在饮用测试前 2 周开始每天用雌二醇苯甲酸酯(EB)或载体处理,并在整个 DID 过程中进行处理。在另一组实验中,在自由循环的小鼠中测量 EtOH 消耗和发情周期阶段,这些小鼠每周 5 天饮用 EtOH 或水 2 或 6 周。
雌性小鼠比雄性和 OVX 小鼠消耗更多的 EtOH。与载体处理的对照组相比,EB 处理增加了 OVX 小鼠的 EtOH 消耗。然而,EtOH 摄入量在发情周期中没有变化,长期 DID 也没有改变发情周期。
这些结果表明,卵巢激素,特别是 E2,有助于 DID 测试中雌性小鼠增加 EtOH 消耗。尽管卵巢激素对此行为有贡献,但在自由循环的小鼠中,EtOH 消耗不受发情周期阶段的影响。这项研究为理解导致女性 binge drinking 的因素提供了框架。