Effects of voluntary exercise on reinstatement of cocaine seeking

描述(由申请人提供)：治疗药物成瘾最具挑战性的方面之一是防止由于日常挑战而复发，如压力或接触药物或与药物相关的线索。尽管进行了多年的研究，但目前还没有普遍接受的药物疗法。有氧运动对身心健康都有好处，提示它也可能是治疗药物依赖的一种有效方法。我们和其他人已经证明，中枢去甲肾上腺素系统的激活对于压力诱导和药物诱导的药物自我给药大鼠模型的恢复是必不可少的。我们还发现，慢性运动增加了去甲肾上腺素能神经元神经肽Galanin的表达，并损害了应激诱导的去甲肾上腺素的释放。这项建议的目的是检验一种假设，即自愿锻炼可以减弱压力诱导和药物诱导的可卡因寻求的恢复。在这项建议的目标1中，我们将确定慢性自愿运动(车轮跑步)是否能钝化应激诱导的或药物诱导的大鼠寻求可卡因的恢复。在目标2中，我们将确定车轮运动诱导蓝斑去甲肾上腺素能区甘丙素表达的幅度与恢复之间是否存在负相关，以及阻断甘丙素信号是否逆转运动的有益效果。在目标3中，我们将进一步研究运动诱导的甘丙素表达和去甲肾上腺素释放之间的相互作用。 与公共卫生相关：吸毒成瘾是一种慢性、复发性疾病，非常难以治疗，给社会带来巨大的社会和经济压力。有氧运动对身心健康有多方面的好处，对药物依赖的治疗可能也有好处。这项建议的目的是评估有氧运动对药物复吸大鼠模型的影响，并探讨潜在的潜在机制。这些实验的完成可能预示着一种治疗药物成瘾的新方法。

DESCRIPTION (provided by applicant): One of the most challenging aspects of treating drug addiction is preventing relapse due to daily challenges such as stress or exposure to drugs or drug-associated cues. Despite many years of research, no generally accepted pharmacotherapy exists. Aerobic exercise has beneficial effects on both physical and mental health, suggesting that it may also be an effective therapy for the treatment of drug dependence. We and others have shown that activation of the central noradrenergic system is essential for stress-induced and drug-primed reinstatement in the rat model of drug self- administration. We have also discovered that chronic exercise increases expression of the neuropeptide galanin in noradrenergic neurons and impairs stress-induced norepinephrine release. The purpose of this proposal is to test the hypothesis that voluntary exercise can attenuate stress-induced and drug-primed reinstatement of cocaine seeking. In Aim 1 of this proposal, we will determine whether chronic voluntary exercise (wheel running) blunts stress-induced or drug-primed reinstatement of cocaine seeking in rats. In Aim 2, we will determine whether a negative correlation exists between the magnitude of wheel running-induced galanin expression in the noradrenergic locus coeruleus and reinstatement, and whether blockade of galanin signaling reverses the beneficial effects of exercise. In Aim 3, we will further investigate the interaction between exercise-induced galanin expression and norepinephrine release. PUBLIC HEALTH RELEVANCE: Drug addiction is a chronic, relapsing disease that is very difficult to treat and places enormous social and economic stress on society. Aerobic exercise is beneficial for many aspects of physical and mental health, and may be beneficial for the treatment of drug dependence. The purpose of this proposal is to assess the effects of aerobic exercise in a rat model of drug relapse, and to investigate potential underlying mechanisms. Completion of these experiments may indicate a new therapy for the treatment of drug addiction.