Estradiol Effects on Behavioral and Reward Sensitivity to Alcohol across the Menstrual Cycle

项目概要/摘要 饮酒会造成严重的健康问题，特别是当大量饮酒时 (i.e.,狂欢）。现在人们认识到，妇女更容易受到下列因素的不利影响： 酒精，包括更大的器官损伤的生理风险（例如，肝硬化），而男性 相似的饮酒史研究表明，卵巢激素在药物滥用中发挥作用。 关于酒精的使用，有证据表明，妇女可能表现出不同的模式， 在月经周期中饮酒事实上，我们的初步研究表明，卵泡雌二醇的激增 [E2]在排卵期预测年轻女性饮酒量增加。然而，到目前为止，还没有任何研究旨在 确定E2快速激增增加滥用可能性的具体行为机制， 酒精这项研究直接检测了卵巢激素流量和对酒精的急性敏感性， 第一次严格和综合测试的假设，迅速上升的雌二醇增加急性奖励 酒精的抑制作用，这种高度的敏感性增加了酒精的使用以外的 实验室100名自然循环妇女的样本将在月经周期内每天使用 激素波动和酒精使用的日常生态评估的综合结合，沿着 战略定时实验室测试他们的急性敏感性的奖励和解除抑制的影响， 控制酒精剂量。这些发现将促进对神经行为机制的理解 将E2与酒精滥用联系起来，并通过强调月经的重要性来告知临床评估实践 评估年轻女性酗酒风险时的周期阶段和激素概况。

PROJECT SUMMARY/ABSTRACT Alcohol use poses significant health problems particularly when characterized by bouts of heavy consumption (i.e., binges). It is now recognized that women demonstrate greater vulnerability to the adverse effects of alcohol, including greater physiological risk of organ damage (e.g., liver cirrhosis), than do men with comparable histories of alcohol use. Research suggests that ovarian hormones play a role in substance abuse. With regard to alcohol use, there is evidence to suggest that women may exhibit distinct patterns of heavy drinking across the menstrual cycle. Indeed, our preliminary research shows that surges in follicular estradiol [E2] at ovulation predict increased alcohol use in young women. Yet, to date no research has aimed to determine the specific behavioral mechanisms by which rapid surges in E2 confer increased abuse potential of alcohol. The proposed study directly examines ovarian hormone flux and acute sensitivity to alcohol to provide the first rigorous and integrative test of the hypothesis that rapid rises in estradiol increase the acute rewarding and disinhibiting effects of alcohol and that this heightened sensitivity increases alcohol use outside the laboratory. A sample of 100 naturally-cycling women will be examined daily over their menstrual cycle using an integrative combination of daily ecological assessments of hormone fluctuations and alcohol use along with strategically-timed laboratory tests of their acute sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol. The findings will advance understanding of the neurobehavioral mechanisms linking E2 to alcohol abuse and inform clinical assessment practice by highlighting the importance of menstrual cycle phase and hormonal profiles when assessing alcohol abuse risk in young women.