Effects of voluntary exercise on reinstatement of cocaine seeking

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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.