The mesolimbic dopaminergic reward pathway is activated by both alcohol and exercise, suggesting exercise as a possible treatment or preventative method for alcohol-use disorders (AUDs). Prior studies conducted in our lab have demonstrated the hedonic substitution of voluntary alcohol consumption for voluntary wheel running in female C57Bl/6Ibg mice, and a trend in male C57Bl/6Ibg mice. Given the important contribution of genetic background on AUDs, this study aims to assess the effects of voluntary wheel running on voluntary alcohol consumption in two moderate alcohol-consuming strains of mice, C3H/Ibg and 129/SvEvTac. Contrary to our previous studies conducted in C57Bl/6Ibg mice, 129/SvEvTac and male C3H/Ibg mice housed without a wheel consumed significantly more alcohol than mice housed with a free or locked wheel. This suggests that 129/SvEvTac and male C3H/Ibg mice are reducing their alcohol consumption due to an enriched environment and not exercise. Interestingly, the three groups of female C3H/Ibg mice (free wheel, locked wheel, no wheel) did not significantly differ in alcohol consumption, suggesting sex-specific differences in C3H/Ibg mice. In addition, genetic and sex effects were observed for running phenotypes in the presence of alcohol. Female 129/SvEvTac and C57Bl/6Ibg mice ran longer distances than male mice, whereas male and female C3H/Ibg mice did not differ in distance run. C3H/Ibg and female 129/SvEvTav mice with access only to water ran longer distances than mice with access to both alcohol and water. However, this effect was not observed in C57Bl/6Ibg or male 129/SvEvTac mice. The results of this mouse model highlight the importance of genetic background and sex on an animal's response to exercise as an enrichment to reduce voluntary alcohol consumption.
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