Exercise-induced changes in impulsivity and cocaine self-administration

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，也可以减少药物使用。然而，这些效应可能发生的机制尚不清楚。这项拟议研究的总体目标是了解锻炼对冲动和药物使用的影响，并确定这些影响是否存在共同的机制。在大鼠身上进行了三个实验，这些实验使用并行结构来增加来自每个数据的能力，以告知对其他数据的解释。实验1(目标1)将确定重复跑步机锻炼(3个水平：不锻炼，20分钟，60分钟)是否与冲动(延迟打折)的减少有关。实验2(目标2)将确定重复体育锻炼是否与可卡因自我给药的较低获得率有关，以及通过检查一系列可卡因剂量的反应率来确定对可卡因增强疗效的敏感性降低。实验3(目标3)将检测反复体育锻炼和对可卡因刺激的反应后伏隔核和前额叶皮质中的多巴胺能活动，因为多巴胺和这些结构在冲动和药物自我给药中已经确定了作用。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，并将提供数据，鼓励临床研究将运动作为青春期和青春期的一种治疗和潜在的预防措施。 与公共健康相关：这些研究将确定定期体育锻炼是否会减少冲动决策，这是引发一些危险、不健康行为的已知风险因素，并降低使用可卡因的可能性。研究还将试图确定这些影响的潜在机制，稍后可能会开发出来，以补充和增加锻炼对这些行为的有效性。

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.