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 #
1R01DA027535-01
Application #
7762683
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
2010-01-15
Budget End
2010-12-31
Support Year
1
Fiscal Year
2010
Total Cost
$393,167
Indirect Cost
Name
Emory University
Department
Genetics
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Schmidt, Karl T; Schroeder, Jason P; Foster, Stephanie L et al. (2017) Norepinephrine regulates cocaine-primed reinstatement via ?1-adrenergic receptors in the medial prefrontal cortex. Neuropharmacology 119:134-140
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
Manvich, Daniel F; Stowe, Taylor A; Godfrey, Jodi R et al. (2016) A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats. Biol Psychiatry 79:940-6
Weinshenker, David; Holmes, Philip V (2016) Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin. Brain Res 1641:320-37
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
Gokhale, Avanti; Vrailas-Mortimer, Alysia; Larimore, Jennifer et al. (2015) Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. Hum Mol Genet 24:5512-23
Sciolino, N R; Smith, J M; Stranahan, A M et al. (2015) Galanin mediates features of neural and behavioral stress resilience afforded by exercise. Neuropharmacology 89:255-64
Shepard, Kathryn N; Liles, L Cameron; Weinshenker, David et al. (2015) Norepinephrine is necessary for experience-dependent plasticity in the developing mouse auditory cortex. J Neurosci 35:2432-7
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
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

Showing the most recent 10 out of 23 publications