Yale SCOR on Gender-Sensitive Treatment for Tobacco Dependence

描述(由申请者提供)：耶鲁-SCOR汇聚了顶尖的基础和临床科学专家，建立了一个跨学科、翻译、跨物种的研究计划，旨在确定新的治疗方法，以解决女性吸烟者面临的严重健康差距。在美国，烟草使用是可预防的发病率和死亡率的主要原因。与男性相比，女性的戒烟率更低，健康风险加剧，FDA批准的戒烟药物可能对女性不那么有效，或者由于副作用而出现限制。然而，很少有人尝试开发对性别敏感的戒烟疗法。大量数据表明，女性更有可能吸烟是为了调节负面情绪和压力，而男性吸烟更有可能是因为尼古丁的强化特性，这表明开发一种新的戒烟方法是一个重要方向。使用临床前和临床策略，我们的跨学科团队将探索去甲肾上腺素系统对应激反应和尼古丁强化的影响-假设(A)受去甲肾上腺素活动调节的不同大脑系统在吸烟时被激活，以及(B)鸟嘌呤(一种α-2a去甲肾上腺素能激动剂)可以优先靶向这些性别敏感的系统，以改善戒烟效果。利用跨学科团队合作的转换方法，我们提出了三个具有相互关联和共同目标的项目，每个项目都为性别敏感疗法的发展做出了独特的贡献。这一新的应用程序将催化耶鲁大学的大量资源，以支持女性健康领域的跨学科和转化科学，以追求极其及时的科学发现，这些发现可能代表着我们对每天影响数百万人的公共卫生问题的治疗方法的理解上的突破。我们耶鲁-SCOR的具体目的和目标是： 目的1：评估去甲肾上腺素系统及其与胆碱和多巴胺能系统的相互作用在应激诱导的吸烟复发和尼古丁强化中的作用，并利用这些发现来指导和加速性别敏感的戒烟疗法的发展。 目标2：指导初级调查人员通过培训机会进行关于烟草使用和妇女健康的跨学科转化性研究，包括提供SCOR PIs的“助理”职位，并提供试点资金。 目标3：成为一个全国性的资源，通过提供专家咨询、支持教师培训奖项、挖掘有关性别、吸烟和健康结果的全国性数据来为卫生政策提供信息，并通过提供专家咨询、支持教师培训奖项、扩大我们当前的地方和国家社区外展计划，来振兴和促进吸烟与性别和性别差异的研究。 公共卫生相关性：与男性相比，女性戒烟率较低，健康风险加剧，但很少有人尝试开发对性别敏感的戒烟疗法。这项研究将通过提供一种神经生物学知情的方法来开发对性别敏感的戒烟疗法，指导下一代跨学科和翻译研究人员，并提供关于妇女健康和烟草使用的国家资源，从而促进公共健康。

DESCRIPTION (provided by applicant): The Yale-SCOR is bringing together leading basic and clinical science experts to establish an interdisciplinary, translational, cross-species program of research aimed at identifying novel therapeutics to address the critical health disparity that female smokers face. Tobacco use is the leading cause of preventable morbidity and mortality in the United States. Women, compared to men, have poorer rates of smoking cessation, exacerbated health risks, and FDA-approved medications for smoking cessation may not be as effective for women or have emerging limits due to side effects. However, few attempts have been made to develop gender-sensitive smoking cessation treatments. The considerable body of data suggesting that women are more likely to smoke to regulate negative affect and stress while men are more likely to smoke for the reinforcing properties of nicotine suggests an important direction in the development of a new approach to smoking cessation treatments. Using both preclinical and clinical strategies, our interdisciplinary team will probe te noradrenergic system's effects on stress-reactivity and nicotine reinforcement -hypothesizing that (a) different brain systems modulated by noradrenergic activity are activated by smoking in women and men, and (b) guanfacine (an alpha-2a noradrenergic agonist) can preferentially target these gender-sensitive systems to improve smoking cessation outcomes. Using a translational approach with an interdisciplinary team effort, we are proposing three projects that will have inter-related and shared goals, with each providing unique contributions to the development of gender-sensitive therapeutics. This new application will catalyze Yale's significant resources to support interdisciplinary and translational science in women's health to pursue extremely timely scientific findings that could represent a breakthrough in our understanding of treatments for a public health problem that affects millions daily. Our specific aims and objectives of the Yale-SCOR are to: AIM 1: Evaluate the role of the noradrenergic system and its interactions with cholinergic and dopaminergic systems, in stress-induced smoking relapse and nicotine-based reinforcement, and use these findings to inform and expedite the development of gender-sensitive therapeutics for smoking cessation. AIM 2: Mentor junior investigators in conducting interdisciplinary translational research on tobacco use and women's health through training opportunities, including "clerkships" with SCOR PIs, and pilot funding. AIM 3: Be a national resource to invigorate and galvanize the study of sex and gender differences in relation to smoking by providing expert consultation; supporting faculty training awards; mining national data on gender, smoking and health outcomes to inform health policy; and expanding our current program of local and national community outreach. PUBLIC HEALTH RELEVANCE: Women compared to men, have poorer rates of smoking cessation and exacerbated health risks yet few attempts have been made to develop gender-sensitive smoking cessation treatments. This research will contribute to the public health by providing a neurobiologically-informed approach to the development of gender-sensitive therapeutics for smoking cessation, mentoring the next generation of interdisciplinary and translational researchers, and providing a national resource for women's health and tobacco use.