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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA027535-04
Application #
8414885
Study Section
Special Emphasis Panel (ZDA1-GXM-A (05))
Program Officer
Lynch, Minda
Project Start
2010-01-15
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$357,122
Indirect Cost
$59,038
Name
Emory University
Department
Genetics
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J et al. (2016) Chronic loss of noradrenergic tone produces ?-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens. Addict Biol 21:35-48
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Schank, Jesse R; King, Courtney E; Sun, Hui et al. (2014) The role of the neurokinin-1 receptor in stress-induced reinstatement of alcohol and cocaine seeking. Neuropsychopharmacology 39:1093-101

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