Sex-Specific Pathways Linking Stress and Drug Abuse

描述（由申请人提供）： 这个K02应用程序寻求支持，这是我作为一个新的独立的临床研究人员继续职业发展必不可少的。由NIH妇女健康研究办公室（ORWH）和NIDA机构培训补助金联合资助（K12-DA 14038; PI：Carolyn Mazure，项目总监：布鲁斯·罗恩萨维尔），我在研究压力与药物滥用之间的关系中的性别差异方面获得了丰富的经验过去3年。我已经展示了相当大的研究生产力，这可以从我的同行评议的出版物中得到证明，我在女性健康专业研究中心（SCOR）的科学指导地位，关于性，压力和可卡因成瘾（P50-DA16556，PI：Sinha），我在两个中心部分的主要和共同主要的顾问，以前的NIDA资助的R01（R01-DA11077，PI：Sinha）和最近授予的R01（AA13892，PI：Sinha）。然而，这一薪金支助来源（75%）将于2003年12月31日到期，因此我寻求另一种筹资机制。因此，这个K02奖对于维持我目前的全职研究重点和促进我发展成为一个完全独立的调查员至关重要。该奖项的理由是提供了一个全面的5年职业发展计划，填补了我目前在压力和药物复吸的神经生物学中性别特异性因素方面的专业知识的重要空白。具体来说，我将获得几个额外的多学科领域的专业技能：（a）压力和药物成瘾的基本性别特异性神经生物学;（B）研究压力和药物渴望状态的药理学和心理学方法;以及（c）先进的生物统计工具，如混合线性模型和随机效应模型。强化培训是通过校内课程、校外教学法、个别指导、互动式专题讨论会和与药物滥用和妇女健康有关的研究组织会议的综合课程提供的。一个代表性的研究项目（P50-DA16556，中心项目PI：R。Sinha），将检查，（1）性别差异的主观，自主神经和HPA反应的压力和药物线索相比，中性线索在可卡因依赖的男性和女性，和（2）性别差异之间的关联早期创伤，紧张的生活事件，急性心理生物学反应的压力和药物线索和可卡因复吸。这个研究项目沿着我正在进行的其他研究，说明了这个职业奖的重大影响，不仅将促进我的科学事业，而且还将促进我们对压力如何增加男性和女性药物复发风险的基本理解。这种认识将对开发针对不同性别的可卡因依赖治疗方法产生重要影响，最终将改善可卡因成瘾妇女及其家人的健康。

DESCRIPTION (provided by applicant): This K02 application seeks support which is essential for my continued career development as a newly independent clinical researcher. Funded by a joint NIH Office of Research on Women's Health (ORWH) and NIDA institutional training grant (K12-DA14038; PI: Carolyn Mazure, Program Director: Bruce Rounsaville), I have attained substantial experience in examining sex differences in the association between stress and drug abuse over the past 3 years. I have demonstrated considerable research productivity as evidenced by my peer-reviewed publications, my scientific directorship of a Women's Health Specialized Center of Research (SCOR) on sex, stress and cocaine addiction (P50-DA16556, PI: Sinha), my principal and co-principal investigatorships on two center sections, a previous NIDA funded R01 (R01-DA11077, PI: Sinha) and a recently awarded R01 (AA13892, PI: Sinha). However, this source of salary support (75%) will expire by 12/31/03, leading me to seek an alternative mechanism of funding. Therefore, this K02 award is vital for sustaining my current full-time research focus and for facilitating my development into a fully independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan that fills important gaps in my current expertise in sex-specific factors in the neurobiology of stress and drug relapse. Specifically, I will acquire specialized skills in several additional multidisciplinary areas: (a) basic sex-specific neurobiology of stress and drug addiction; (b) pharmacological and psychological methods to study stress and drug craving states; and (c) advanced bio-statistical tools such as mixed linear models and random effects models. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings on drug abuse and women's health. A representative research project (P50-DA16556, Center Project PI: R. Sinha) is included, which will examine, (1) sex differences in the subjective, autonomic and HPA response to stress and to drug cues as compared to neutral cues in cocaine dependent men and women, and (2) sex differences in the association between early trauma, stressful life events, acute psychobiological responses to stress and to drug cues and cocaine relapse. This research project along with additional lines of research that I am conducting illustrates the significant impact this career award will have in furthering not only my scientific career, but also our fundamental understanding of how stress increases the risk of drug relapse differentially in men and women. Such an understanding will have important implications for the development of gender-specific treatments for cocaine dependence that will ultimately improve the health of cocaine-addicted women and their families.