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的方法来研究性别差异、荷尔蒙状态(例如，孕酮前体)、冲动和药物动机行为之间正在出现的和潜在的重要互动，这些互动可能对减少吸烟和可卡因滥用这两种毁灭性的药物滥用产生重要后果。中心假设是，减少冲动将减少寻求毒品的行为。黄体酮可降低冲动，与有类似作用的药物(如阿托莫西汀-ATO)联合使用，可显著减少尼古丁和可卡因的摄入量 滥用可能会被实现。PRO还将与显示出对尼古丁依赖有一定效果的药物--动物项目中的varenicline(VAR)--一起进行测试。根据越来越多关于药物滥用的性别差异的文献，单一治疗和联合治疗的效果可能存在性别差异。以下是《公约》的具体目标： 1.在临床研究项目1中，比较外源性PRO与安慰剂在冲动和戒烟方面的性别差异。 2.在临床研究项目2中，研究外源性PRO与安慰剂合用与安慰剂在冲动和复吸可卡因方面的性别差异。 3.观察PRO单独及联合应用ATO和VAR后尼古丁和可卡因复吸动物模型的性别差异以及对尼古丁和可卡因的冲动性。另一个目标是研究怀孕(高PRO)和哺乳期(低PRO)的怀孕大鼠与雄性和未怀孕的雌性大鼠相比，内源性PRO对尼古丁或可卡因自我给药的影响。这一SCOR允许采用跨学科和转换的方法来实现这些目标。它还提供了经济效率，提供了与参与SCOR的其他人交流想法和方法的机会。

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.