Evidence for a long-term protection of wheel-running exercise against cocaine psychomotor sensitization in adolescent but not in young adult mice

Abstract

Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of the exercise anti-drug protection and the influence of the developmental stage during which exercise is displayed received little attention. Here, females and males C57BL/6J mice, aged 28 (adolescents) or 77 (young adults) days were housed with (n=56) or without (n=28) a running wheel. After 3 weeks in these conditions, half of the exercised mice were deprived of their wheel (n=28) whereas the other half and the sedentary mice (no wheel) were kept in their respective environments throughout experimentation. After 3 additional weeks, mice were tested for initiation of psychomotor sensitization to 9 once-daily intraperitoneal injections of 8 mg/kg cocaine (following 2 drug-free test sessions). The expression of sensitization was assessed on a single test session 30 days after the last sensitizing cocaine injection. Continuously exercised mice (wheel throughout experimentation) were less responsive to the initiation and the expression of cocaine effects, regardless of the gender and the developmental period during which exercise was introduced. Wheel-running during adolescence attenuated in later life the initiation and the expression of sensitization in females and only its expression in males. In adult females and males, previously-exercised and sedentary mice exhibited indiscernible levels of initiation and expression of sensitization. Thus, the likelihood of the long-term protection of exercise against cocaine vulnerability may depend not only on the gender but also and especially on the period of life in which exercise took place.