Long-term effects of exercise during youth or adulthood on cocaine reactivity in mice: qualitative developmental differences

Epidemiological studies suggest that physical exercise could have preventive properties on drugs vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of physical exercise) can exhibit attenuated drug seeking and drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. Objectives: the aim was to evaluate the longevity of the protective effects of exercise on cocaine vulnerability and the influence of the developmental stage during which exercise is applied (in 4 experiments). Method: females and males C57BL/6J mice, aged 28 (youth) or 77 days (adults) were housed with (n=56) or without (n=28) a running wheel. After 3 weeks, half of the exercised mice (n=28) were deprived of their wheel (3 housing conditions/experiment). Three weeks later, mice were tested for sensitization to the psychomotor-activating effects of 8 mg/kg cocaine over 9 once-daily sessions (controls: saline solution). Mice were also tested 30 days later for their long-term expression of sensitization. Results: continuous wheel-running housing reduced cocaine responsiveness in both females and males regardless of the age on which exercise was introduced. Exercise performed exclusively in youth, but not over adulthood, reduced durably cocaine responsiveness, particularly in females. Conclusion: the likelihood of the long-term protection of exercise against cocaine responsiveness may depend on the age of exercise application and the gender.