Sex-Appropriate Treatment Development for Alcohol Use Disorders

摘要：对于这个项目，我们聚集了一支成功的基础和临床科学专家团队，致力于寻找新的治疗方法，以应对最近女性酒精使用障碍(AUD)发病率的激增。在过去的10年里，女性的AUD比率增加了84%，相当于全美有1050万女性。在美国，饮酒是可预防的发病率和死亡率的第三大原因，与男性相比，女性饮酒者的健康风险更大。FDA批准的治疗AUD的药物具有低到中等的疗效，并且没有针对维持女性饮酒的因素。大量数据表明，女性饮酒更有可能是为了调节负面情绪和压力，而男性饮酒更有可能是为了强化酒精相关的积极作用。在我们的三个项目中，我们将探索去甲肾上腺素系统对应激反应和酒精强化的影响。我们的主要目的是评估去甲肾上腺素系统的作用，以靶向已知在女性与男性之间维持酒精使用的性别依赖因素，并评估瓜那法辛作为一种典型药物，优先针对这些性别依赖因素，以改善AUD的治疗结果。

Abstract: For this program project we bring together a successful team of leading basic and clinical science experts to pursue research aimed at identifying novel therapeutics to address the recent surge in rates of alcohol use disorders (AUD) in women. Over the past 10 years, rates of AUD in women have increased by 84%, translating to 10.5 million women across the United States. Alcohol use is the third leading cause of preventable morbidity and mortality in the United States and women drinkers experience exacerbated health risks associated with alcohol consumption when compared to men. FDA-approved medications for AUD have low to moderate efficacy and none target factors that maintain drinking in women. A considerable body of data identifies that women are more likely to drink to regulate negative affect and stress, while men are more likely to drink for alcohol-related positive reinforcement. Across our three Projects, we will probe the noradrenergic system’s effects on stress reactivity and alcohol reinforcement. Our primary aim is to evaluate the role of the noradrenergic system to target sex-dependent factors known to maintain alcohol use in women versus men and to evaluate guanfacine as a prototypical medication to preferentially target these sex-dependent factors to improve AUD treatment outcomes.