Abstract
Rationale
Voluntary aerobic exercise has shown promise as a treatment for substance abuse, reducing relapse in cocaine-dependent people. Wheel running also attenuates drug-primed and cue-induced reinstatement of cocaine seeking in rats, an animal model of relapse. However, in most of these studies, wheel access was provided throughout cocaine self-administration and/or extinction and had effects on several parameters of drug seeking. Moreover, the effects of exercise on footshock stress-induced reinstatement have not been investigated.
Objectives
The purposes of this study were to isolate and specifically examine the protective effect of exercise on relapse-like behavior elicited by a drug prime or stress.
Methods
Rats were trained to self-administer cocaine at a stable level, followed by extinction training. Once extinction criteria were met, rats were split into exercise (24 h, continuous access to running wheel) and sedentary groups for 3 weeks, after which, drug-seeking behavior was assessed following a cocaine prime or footshock. We also measured galanin messenger RNA (mRNA) in the locus coeruleus and A2 noradrenergic nucleus.
Results
Exercising rats ran ∼4–6 km/day, comparable to levels previously reported for rats without a history of cocaine self-administration. Post-extinction exercise significantly attenuated cocaine-primed, but not footshock stress-induced, reinstatement of cocaine seeking, and increased galanin mRNA expression in the LC but not A2.
Conclusion
These results indicate that chronic wheel running can attenuate some forms of reinstatement, even when initiated after the cessation of cocaine self-administration, supporting the idea that voluntary exercise programs may help maintain abstinence in clinical populations.
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Acknowledgments
We thank Cheryl Strauss for the helpful editing of the manuscript. This work was supported by the National Institute of Drug Abuse (DA027535 to DW and PVH, DA033091 and DA015040 to YEO).
Conflict of interest
DW is co-inventor on a patent concerning the use of selective dopamine β-hydroxylase inhibitors for the treatment of cocaine dependence (US-2010-0105748-A1; “Methods and Compositions for Treatment of Drug Addiction”). The other authors declare no conflicts of interest.
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Ogbonmwan, Y.E., Schroeder, J.P., Holmes, P.V. et al. The effects of post-extinction exercise on cocaine-primed and stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology 232, 1395–1403 (2015). https://doi.org/10.1007/s00213-014-3778-9
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DOI: https://doi.org/10.1007/s00213-014-3778-9