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，也可以减少吸毒。然而，这些效应发生的机制尚不清楚。这项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的机制。在大鼠中提出了三个实验，使用并行结构来增加来自每个结构的数据的能力，从而为解释其他结构提供信息。实验1（目的1）将确定重复的跑步机运动（3个水平：不运动，20分钟，60分钟）是否与冲动性的降低有关（延迟折扣）。实验2（目标2）将确定反复体育锻炼是否与较低的可卡因自我给药获得率有关，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强化功效的敏感性降低。实验3（目的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叶皮层的多巴胺能活动，因为多巴胺和这些结构在冲动和药物自我给药中已经确立了作用。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，并将提供数据，可以刺激临床研究，检查运动作为青春期和青年期的治疗和潜在预防措施。

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.