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预防由于日常挑战（如压力或暴露于药物或药物相关线索）而导致的复发。尽管多年的研究，没有普遍接受的药物治疗存在。有氧运动对身体和心理健康都有有益的影响，这表明它也可能是治疗药物依赖的有效疗法。我们和其他人已经表明，中枢去甲肾上腺素能系统的激活对于大鼠自我给药模型中应激诱导和药物引发的恢复是必不可少的。我们还发现，慢性运动增加去甲肾上腺素能神经元中神经肽甘丙肽的表达，并损害应激诱导的去甲肾上腺素释放。这项建议的目的是测试的假设，自愿行使可以减弱压力引起的和药物引发的恢复可卡因寻求。在本提案的目标1中，我们将确定慢性自愿运动（轮跑）是否会减弱大鼠中压力诱导或药物引发的可卡因寻求恢复。在目标2中，我们将确定是否存在负相关的车轮运行诱导的甘丙肽表达的去甲肾上腺素能蓝斑和恢复之间的幅度，以及是否阻断甘丙肽信号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肽表达和去甲肾上腺素释放之间的相互作用。 公共卫生相关性：吸毒成瘾是一种慢性复发性疾病，很难治疗，给社会带来巨大的社会和经济压力。有氧运动有益于身心健康的许多方面，并可能有益于药物依赖的治疗。本研究的目的是评估有氧运动对大鼠药物复吸模型的影响，并探讨其潜在的机制。这些实验的完成可能预示着一种治疗药物成瘾的新疗法。

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.