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

项目摘要/摘要 饮酒会造成严重的健康问题，特别是在以大量饮酒为特征的时候 (即暴饮暴食)。现在人们认识到，妇女更容易受到艾滋病的不利影响 酒精，包括更大的器官损害的生理风险(例如，肝硬变)，比男性 有类似的饮酒史。研究表明，卵巢激素在物质滥用中起着一定作用。 关于饮酒，有证据表明，女性可能会表现出明显的酗酒模式 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]在排卵时预测年轻女性饮酒量增加。然而，到目前为止，还没有研究旨在 确定特定的行为机制，通过这些机制，雌二醇会增加滥用的可能性 酒精。这项拟议的研究直接检查卵巢激素的流动和对酒精的急性敏感性，以提供 首次对雌激素快速上升增加急性回报这一假设进行了严格的综合检验 以及酒精的抑制作用，这种高度的敏感性增加了人们在户外的酒精使用量 实验室。100名自然骑自行车的女性样本将在她们的月经周期内每天接受检查，使用 对荷尔蒙波动和酒精使用的日常生态评估以及 战略性地定时进行实验室测试，以确定它们对 控制剂量的酒精。这一发现将促进对神经行为机制的理解 通过强调月经的重要性，将雌二醇与酒精滥用联系起来，并为临床评估实践提供信息 在评估年轻女性酗酒风险时的周期时相和荷尔蒙分布。

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.