Sex Differences and Progesterone Effects on Impulsivity, Smoking & Cocaine Abuse

描述（由申请人提供）：本SCOR的目标是采用跨学科方法研究性别差异、激素状态（例如，孕酮（PRO），冲动和药物动机的行为，这可能对减少两种破坏性形式的药物滥用，吸烟和可卡因滥用产生重要影响。核心假设是，减少冲动会减少寻求毒品的行为。Progressive减少冲动，并与具有类似效果的药物（例如，托莫西汀- ATO），尼古丁和可卡因显著减少 可以实现滥用。PRO还将与显示对尼古丁依赖有一定影响的药物，varenicline（VAR）一起在动物项目中进行测试。根据越来越多的关于药物滥用性别差异的文献，单一和联合治疗的效果可能存在性别差异。委员会的具体目标如下： 1.在临床项目1中，研究外源性PRO与安慰剂相比对冲动和戒烟影响的性别差异。 2.在临床项目2中研究外源性PRO与安慰剂联合ATO与安慰剂对可卡因滥用冲动性和复发影响的性别差异。 3.检查PRO单独给药以及与ATO和VAR联合给药的大鼠中尼古丁和可卡因复发以及尼古丁或可卡因冲动的动物模型中的性别差异。另一个目标是研究与雄性和未妊娠雌性相比，妊娠大鼠在妊娠（高PRO）和哺乳（低PRO）期间内源性PRO对尼古丁或可卡因自我给药的影响。这SCOR允许跨学科和翻译的方法来实现这些目标。它还提供了经济效率，与参与SCOR的其他人交流想法和方法的机会。 公共卫生相关性：尽管付出了很大努力，但目前还没有高效的批准药物用于直接治疗可卡因和尼古丁依赖。该SCOR将开展跨学科和转化研究，以确定针对尼古丁和可卡因依赖受试者行为受损的药理干预措施，以提高现有成瘾行为治疗的有效性。

DESCRIPTION (provided by the applicant): The goal of this SCOR is to take an interdisciplinary approach to studying an emerging and potentially important interaction between sex differences, hormonal status (e.g., progesterone - PRO), impulsivity, and drug-motivated behavior that could have important consequences for reducing two devastating forms of drug abuse, cigarette smoking and cocaine abuse. The central hypothesis is that reducing impulsivity will reduce drug-seeking behavior. Progesterone reduces impulsivity, and combined with drugs that have similar effects (e.g., atomoxetine - ATO), significant reductions in nicotine and cocaine abuse may be achieved. PRO will also be tested in combination with drugs that show some effect for nicotine dependence, varenicline (VAR) in the animal project. Based on a growing literature on sex differences in drug abuse, there may be sex differences in the effect of single and combined treatments. The following are the Specific Aims of the SCOR: 1. Investigate sex differences in the effect of exogenous PRO compared to placebo on impulsivity and smoking cessation in clinical Project 1. 2. To study sex differences in the effect of exogenous PRO vs. placebo in combination with ATO vs. placebo on impulsivity and relapse to cocaine abuse in clinical Project 2. 3. To examine sex differences in an animal model of nicotine and cocaine relapse and impulsivity for nicotine or cocaine in rats treated with PRO alone and in combination with ATO and VAR. Another goal is to study endogenous PRO effects on nicotine or cocaine self-administration in pregnant rats during gestation (high PRO) and lactation (low PRO) compared with males and no pregnant females. This SCOR allows for an interdisciplinary and translational approach to accomplishing these aims. It also offers economic efficiency, an opportunity to exchange ideas and approaches with others who are involved with the SCOR. PUBLIC HEALTH RELEVANCE: Despite much effort, there are not yet highly effective approved medications for the direct treatment of cocaine and nicotine dependence. This SCOR will carry out interdisciplinary and translational investigations to identify pharmacological interventions targeting behaviors impaired in nicotine and cocaine dependent subjects to enhance the effectiveness of existing behavioral treatments for addiction.