Yale SCOR on Gender-Sensitive Treatment for Tobacco Dependence

耶鲁大学 SCOR 关于对烟草依赖进行性别敏感治疗

• 批准号: 8345893
• 负责人: SHERRY ANN MCKEE
• 金额: $ 122.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8345893
• 关键词: Yale; SCOR; Gender; Sensitive; Treatment

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.

耶鲁-SCOR正在汇集领先的基础和临床科学专家，建立一个跨学科，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。烟草使用是美国可预防的发病率和死亡率的主要原因。与男性相比，女性的戒烟率较低，健康风险加剧，FDA批准的戒烟药物可能对女性无效，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治疗。大量数据表明，女性更有可能吸烟以调节负面影响和压力，而男性更有可能吸烟以增强尼古丁的特性，这表明了开发戒烟治疗新方法的重要方向。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能系统对应激反应和尼古丁强化的影响-假设（a）女性和男性吸烟激活了受去甲肾上腺素能活性调节的不同大脑系统，（B）胍法辛（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系统，以改善戒烟结果。使用跨学科团队努力的转化方法，我们提出了三个项目，这些项目将具有相互关联和共同的目标，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重要资源，以支持跨学科和翻译科学在妇女的健康追求非常及时的科学发现，可以代表我们的治疗方法的突破，每天影响数百万人的公共卫生问题。我们的具体目标和耶鲁-SCOR的目标是： 目标1：评估去甲肾上腺素能系统的作用及其与胆碱能和多巴胺能系统的相互作用，在压力诱导的吸烟复吸和尼古丁为基础的强化，并使用这些发现，以通知和加快性别敏感的戒烟疗法的发展。 目标2：通过培训机会，包括与SCOR PI的“见习”和试点资金，指导初级研究人员进行关于烟草使用和妇女健康的跨学科转化研究。 目标3：成为一个国家资源，通过提供专家咨询来激励和激励与吸烟有关的性别和性别差异的研究;支持教师培训奖;挖掘关于性别，吸烟和健康结果的国家数据，以告知卫生政策;并扩大我们目前的地方和国家社区外展计划。 公共卫生关系：与男性相比，女性的戒烟率更低，健康风险更大，但很少尝试开发对性别敏感的戒烟治疗方法。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，并为妇女健康和烟草使用提供国家资源，从而为公共卫生做出贡献。