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.
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.
|Ogbonmwan, Yvonne E; Sciolino, Natale R; Groves-Chapman, Jessica L et al. (2015) The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex. Addict Biol 20:701-13|
|Ogbonmwan, Yvonne E; Schroeder, Jason P; Holmes, Philip V et al. (2015) The effects of post-extinction exercise on cocaine-primed and stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 232:1395-403|
|Schmidt, Karl T; Weinshenker, David (2014) Adrenaline rush: the role of adrenergic receptors in stimulant-induced behaviors. Mol Pharmacol 85:640-50|
|Cooper, Debra A; Kimmel, Heather L; Manvich, Daniel F et al. (2014) Effects of pharmacologic dopamine ?-hydroxylase inhibition on cocaine-induced reinstatement and dopamine neurochemistry in squirrel monkeys. J Pharmacol Exp Ther 350:144-52|
|Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J et al. (2014) Chronic loss of noradrenergic tone produces ?-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens. Addict Biol :|
|Mitrano, D A; Pare, J-F; Smith, Y et al. (2014) D1-dopamine and ?1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex. Neuroscience 258:90-100|
|Epps, S Alisha; Kahn, Alexa B; Holmes, Philip V et al. (2013) Antidepressant and anticonvulsant effects of exercise in a rat model of epilepsy and depression comorbidity. Epilepsy Behav 29:47-52|
|Manvich, Daniel F; DePoy, Lauren M; Weinshenker, David (2013) Dopamine *-hydroxylase inhibitors enhance the discriminative stimulus effects of cocaine in rats. J Pharmacol Exp Ther 347:564-73|
|Schroeder, Jason P; Epps, S Alisha; Grice, Taylor W et al. (2013) The selective dopamine *-hydroxylase inhibitor nepicastat attenuates multiple aspects of cocaine-seeking behavior. Neuropsychopharmacology 38:1032-8|