title: Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats.
abstract: 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.
authors.affiliation: Graduate Program in Neuroscience, Jackson Hall, 321 Church Street SE, University of MN, Minneapolis, MN 55455, USA; Department of Psychiatry, Diehl Hall, 505 Essex Street SE, University of MN, Minneapolis, MN 55455, USA. Electronic address: zleb0002@umn.edu.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Zlebnik
authors.affiliation: Department of Neuroscience, Jackson Hall, 321 Church Street SE, University of MN, Minneapolis, MN 55455, USA.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Hedges
authors.affiliation: Department of Psychiatry, Diehl Hall, 505 Essex Street SE, University of MN, Minneapolis, MN 55455, USA.
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Carroll
authors.affiliation: Department of Neuroscience, Jackson Hall, 321 Church Street SE, University of MN, Minneapolis, MN 55455, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Meisel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012420:Running / Q000502:physiology*; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D003042:Cocaine
keywords: Cocaine; Environmental enrichment; Exercise; Reward; Wheel running; c-Fos