Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats

Natalie E. Zlebnik, Valerie L. Hedges, Marilyn E. Carroll, Robert L. Meisel

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15. mg/kg, i.p.) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalBehavioural Brain Research
StatePublished - Mar 5 2014

Bibliographical note

Funding Information:
National Institute on Drug Abuse (NIDA) grants R01 DA 013680 (RLM) , R01 DA003240 (MEC) , and K05 DA015267 (MEC) supported this research. The authors would like to thank Paul Regier and Alex Claxton for technical assistance.


  • C-Fos
  • Cocaine
  • Environmental enrichment
  • Exercise
  • Reward
  • Wheel running


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