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: 8132984
• 负责人: SUZANNE H MITCHELL
• 金额: $ 18.49万
• 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/8132984
• 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; Human; Impulsive Behavior; Impulsivity; Individual Differences; Infusion procedures; Injection of therapeutic agent; Light; Maintenance; Measures; Microdialysis; Modeling; Nucleus Accumbens; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Rattus; Research; Rewards; Risk Factors; Role; Running; Self Administration; Self-Administered; Structure; Training; Translating; cocaine use; discounting; experience; in vivo; interest; neurobiological mechanism; neurochemistry; prophylactic; public health relevance; research study; response; young adult

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，也可以减少药物的使用。然而，这些影响发生的机制尚不清楚。拟议研究的总体目标是了解运动对冲动和药物使用的影响，并确定这些影响是否存在共同机制。提出了在大鼠中进行的三个实验，这些实验使用并行结构来提高每个实验的数据解释其他实验的能力。实验 1（目标 1）将确定重复的跑步机锻炼（3 个级别：无锻炼、20 分钟、60 分钟）是否与冲动性降低（延迟折扣）相关。实验 2（目标 2）将确定重复的体育锻炼是否与较低的可卡因自我给药获取率相关，以及通过检查可卡因剂量范围内的反应率来确定可卡因增强功效的敏感性降低。实验 3（目标 3）将检查反复体育锻炼和对可卡因挑战的反应后伏隔核和前额皮质的多巴胺能活性，因为多巴胺和这些结构在冲动和药物自我给药中发挥了作用。这项研究将揭示运动可能影响药物使用的神经生物学和行为机制，并将提供可以刺激临床研究的数据，以检验运动作为青春期和青年期的治疗和潜在预防措施。 公共健康相关性：这些研究将确定定期进行体育锻炼是否会减少冲动决策（这是引发许多危险、不健康行为的已知风险因素），并降低使用可卡因的可能性。研究还将尝试找出这些影响背后的机制，稍后可以开发该机制来补充和提高运动对这些行为的有效性。