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

性别差异和黄体酮对冲动、吸烟的影响

基本信息

批准号：
8708809
负责人：
Marilyn E. Carroll
金额：
$ 118.21万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8708809
关键词：
Animal Model Animals Anti-Anxiety Agents Behavior Therapy Behavioral Centers for Disease Control and Prevention (U.S.)Chronic Clinical Clinical Research Cocaine Cocaine Abuse Cocaine Dependence Combined Modality Therapy Data Drug Combinations Drug abuse Economics Effectiveness Estrogens Female Goals Hormonal Human Impulsive Behavior Impulsivity Intervention Investigation Laboratory Animals Lactation Lead Literature Luteal Phase Measures Modeling Monkeys Nicotine Nicotine Dependence Oral Contraceptives Pharmaceutical Preparations Placebos Postpartum Period Pregnancy Principal Investigator Proestrus Progesterone Rattus Relapse Reporting Risk Self Administration Severities Sex Characteristics Smoker Smoking Testing Wit Woman addiction atomoxetine base behavioral impairment cigarette smoking cocaine use comparative drug relapse drug seeking behavior innovation interdisciplinary approach male men motivated behavior nicotine abuse preclinical study pregnant smoking cessation translational approach treatment response treatment strategy varenicline young adult

项目摘要

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.

描述（由申请人提供）：该 SCOR 的目标是采用跨学科方法来研究性别差异、荷尔蒙状态（例如黄体酮 - PRO）、冲动性和药物驱动行为之间新兴且潜在重要的相互作用，这些相互作用可能导致对于减少吸烟和可卡因滥用这两种破坏性形式的药物滥用具有重要影响。中心假设是减少冲动会减少寻求药物的行为。黄体酮可降低冲动性，与具有类似作用的药物（例如阿托莫西汀 - ATO）联合使用，可显着减少尼古丁和可卡因滥用可能会实现。 PRO 还将在动物项目中与对尼古丁依赖显示出一定效果的药物伐尼克兰 (VAR) 结合进行测试。根据越来越多关于药物滥用性别差异的文献，单一治疗和联合治疗的效果可能存在性别差异。以下是 SCOR 的具体目标： 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的影响的性别差异。 2. 在临床项目 2 中研究外源性 PRO 与安慰剂联合 ATO 与安慰剂对冲动性和可卡因滥用复发的影响的性别差异。 3. 在单独使用 PRO 以及与 ATO 和 VAR 联合治疗的大鼠中，检查尼古丁和可卡因复发以及对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怀孕雌性相比，内源性 PRO 对妊娠期（高 PRO）和哺乳期（低 PRO）怀孕大鼠自我施用尼古丁或可卡因的影响。该 SCOR 允许采用跨学科和转化方法来实现这些目标。它还提供经济效益，以及与参与 SCOR 的其他人交流想法和方法的机会。