Effects of voluntary exercise on reinstatement of cocaine seeking

自愿锻炼对恢复可卡因寻求的影响

基本信息

批准号：
8585045
负责人：
PHILIP V HOLMES
金额：
$ 34.92万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-15 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8585045
关键词：
Abstinence Adrenergic Agents Aerobic Exercise Affect Animal Model Attenuated Autoreceptors Brain Brain region Cell Nucleus Chronic Cocaine Cocaine Dependence Cues Drug Addiction Drug Exposure Drug abuse Economics Exercise Exposure to Extinction (Psychology)Feeling Galanin Gene Expression Human In Situ Hybridization Individual Infusion procedures Injection of therapeutic agent Intravenous infusion procedures Investigation Link Mediating Medical Mental Health Messenger RNA Microdialysis Modeling Monkeys Neurons Neuropeptides Norepinephrine Pathway interactions Pharmaceutical Preparations Pharmacotherapy Phase Physical activity Prevention Process Prosencephalon Rattus Recurrent disease Regimen Relapse Research Resistance Reverse Transcriptase Polymerase Chain Reaction Rewards Rodent Model Role Running Self Administration Shock Signal Transduction Societies Stimulus Stress System Testing Time Training Treatment outcome Up-Regulation acute stress adrenergic animal data drug relapse drug seeking behavior effective therapy foot galanin receptor human relapse improved in vivo inhibitor/antagonist insight locus ceruleus structure neuromechanism noradrenergic novel physical conditioning prevent psychologic public health relevance research study response reward circuitry sedentary social substance abuse prevention transmission process

项目摘要

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.

描述（由申请人提供）：治疗药物成瘾的最具挑战性的方面之一是由于每天的挑战，例如压力或暴露于药物或药物相关的提示。尽管进行了多年的研究，但尚无公认的药物治疗。有氧运动对身心健康都有有益的影响，这表明这也可能是治疗药物依赖性的有效疗法。我们和其他人表明，中央去甲肾上腺素能系统的激活对于药物自我给药的大鼠模型中的压力诱导和药物剂的恢复至关重要。我们还发现，慢性运动增加了去甲肾上腺素能神经元中神经肽葡萄蛋白的表达，并损害了压力诱导的去甲肾上腺素的释放。该提案的目的是检验以下假设：自愿运动可以减轻对可卡因寻求的压力引起的和药物染色的恢复。在该提案的目标1中，我们将确定长期自愿运动（车轮运行）是否会钝化了应力引起的可卡因在大鼠中寻求可卡因的恢复。在AIM 2中，我们将确定在去甲肾上腺素能基因座中的车轮运行诱导的Galanin表达和恢复原位之间是否存在负相关，以及封闭Galanin信号传导的阻断是否会逆转运动的有益效果。在AIM 3中，我们将进一步研究运动诱导的Galanin表达和去甲肾上腺素释放之间的相互作用。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Galanin mediates features of neural and behavioral stress resilience afforded by exercise.

DOI：
10.1016/j.neuropharm.2014.09.029
发表时间：
2015-02
期刊：
Neuropharmacology
影响因子：
4.7
作者：
Sciolino NR;Smith JM;Stranahan AM;Freeman KG;Edwards GL;Weinshenker D;Holmes PV
通讯作者：
Holmes PV

The role of the neurokinin-1 receptor in stress-induced reinstatement of alcohol and cocaine seeking.

神经激肽-1 受体在压力诱导的酒精和可卡因恢复中的作用。

DOI：
10.1038/npp.2013.309
发表时间：
2014
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Schank,JesseR;King,CourtneyE;Sun,Hui;Cheng,Kejun;Rice,KennerC;Heilig,Markus;Weinshenker,David;Schroeder,JasonP
通讯作者：
Schroeder,JasonP

Exercise offers anxiolytic potential: a role for stress and brain noradrenergic-galaninergic mechanisms.