Exercise-induced changes in impulsivity and cocaine self-administration

运动引起的冲动和可卡因自我给药的变化

• 批准号: 7763302
• 负责人: SUZANNE H MITCHELL
• 金额: $ 19.25万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7763302
• 关键词: Adolescence; Affect; Animal Model; Animals; Behavior; Behavioral; Behavioral Mechanisms; Clinical Research; Cocaine; Corpus striatum structure; Data; Decision Making; Dopamine; Dose; Drug usage; Effectiveness; Exercise; Future; Human; Impulsive Behavior; Impulsivity; Individual Differences; Infusion procedures; Injection of therapeutic agent; Light; Maintenance; Measures; Microdialysis; Modeling; Neurobiology; Nucleus Accumbens; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Rattus; Research; Rewards; Risk Factors; Role; Running; Self Administration; Self-Administered; Structure; Training; Translating; cocaine use; discount; discounting; experience; in vivo; interest; neurochemistry; prophylactic; public health relevance; research study; response

DESCRIPTION (provided by applicant): Limited data suggest that physical exercise can reduce impulsivity and can also reduce drug use. However, the mechanism by which these effects may occur is unknown. The overall aim of the proposed research is to understand the effects of exercise on impulsivity and drug use, and to determine whether there is a common mechanism underlying these effects. Three experiments are proposed in rats that use parallel structures to increase the ability of data from each to inform interpretation of the others. Experiment 1 (Aim 1) will determine whether repeated treadmill exercise (3 levels: no exercise, 20 min, 60 min) is associated with decreases in impulsivity (delay discounting). Experiment 2 (Aim 2) will determine whether repeated physical exercise is associated with lower rates of acquisition of cocaine self-administration, and a reduction in sensitivity to the reinforcing efficacy of cocaine determined by examining response rates over a range of cocaine doses. Experiment 3 (Aim 3) will examine the dopaminergic activity in the nucleus accumbens and prefrontal cortex following repeated physical exercise and response to a cocaine challenge, as dopamine and these structures have established roles in impulsivity and in drug self-administration. This research will shed light on the neurobiological and behavioral mechanisms by which exercise might influence drug use, and will provide data that can stimulate clinical studies examining exercise both as a treatment and as a potential prophylactic during adolescence and young adulthood. PUBLIC HEALTH RELEVANCE: The studies will determine whether engaging in regular physical exercise decreases impulsive decision-making, which is a known risk factor for initiating a number of dangerous, unhealthy behaviors, and decreases the likelihood of using cocaine. Studies will also try to identify a mechanism underlying these effects, which could be developed later to supplement and increase the effectiveness of exercise on these behaviors.

描述（由申请人提供）：有限的数据表明，体育锻炼可以减少冲动性，也可以减少药物使用。但是，这些影响可能发生的机制尚不清楚。拟议研究的总体目的是了解运动对冲动性和药物使用的影响，并确定这些作用是否存在共同的机制。在使用平行结构来提高每个数据的能力以告知其他人的解释的能力的大鼠中提出了三个实验。实验1（AIM 1）将确定重复的跑步机运动（3级：无运动，20分钟，60分钟）与冲动性下降（延迟打折）有关。实验2（AIM 2）将确定重复的体育锻炼是否与可卡因自我给药的获取率较低有关，以及对可卡因增强可卡因疗效的敏感性降低，通过在一系列可卡因剂量的范围内检查反应率。实验3（AIM 3）将在反复进行体育锻炼和对可卡因挑战的反应后检查伏伏核和前额叶皮质的多巴胺能活性，因为多巴胺和这些结构在冲动性和药物自我管理中已经确立了作用。这项研究将阐明运动可能影响药物使用的神经生物学和行为机制，并提供可以刺激临床研究的数据，以研究运动作为治疗，并在青春期和成年期间作为一种潜在的预防性。 公共卫生相关性：研究将确定进行定期体育锻炼是否会减少冲动性决策，这是启动许多危险，不健康行为的已知风险因素，并降低了使用可卡因的可能性。研究还将尝试确定这些作用的基础机制，以后可以开发出来，以补充和提高锻炼对这些行为的有效性。