Wheel-running exercise during adolescence does not substantially affect cocaine conditioned place preference in male C57BL/6J mice

Epidemiological studies suggest that physical exercise could have preventive properties against drugs of abuse vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of aerobic exercise) can exhibit attenuated drug self-administration or drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. However, the few experiments using conditioned place preference (CPP) are conflicting (positive, negative or null effects of exercise). Aspects or deficiencies of the methods used in some studies, in particular the low sample size (median n=8), the absence of a baseline pre-conditioning session or a control group in the design or (when present) in the data analyses, make the whole picture of results difficult to understand, a situation which warrants further studies, possibly of a better quality than the previous ones. Objectives. Our purpose was to test whether wheel-running exercise during adolescence could impact the formation and long-term retention of CPP to cocaine in mice. Method. Male C57BL/6J mice were individually housed either with (n=32) or without (n=32) a running wheel from 35 days of age. Behavioral testing begun 3 weeks after such housing, all animals being first tested under saline for their baseline preference (white or black compartments). Then, mice underwent 10 once-daily conditioning sessions receiving peritoneal injections of 10 mg/kg cocaine and saline on alternate days (n=16). The white compartment (always non-preferred) was systematically associated to cocaine effects. Control mice received saline every day (n=16). One and 21 days after the last conditioning session, mice were tested for place preference under saline. CPP scores were analyzed with a priori single (cocaine vs saline) and crossed contrasts (testing the housing-by-drug interaction). Each contrast (t-test) incorporated the mean-square error (MSE) provided by a preliminary two-way fixed-model 2x2 ANOVA incorporating the housing condition (2 levels) and the drug treatment (2 levels) as between-group factors and time of testing as a blocking factor (8 levels). Estimates of effect sizes were provided by Cohen’s d calculated from ts and degree of freedom. Results. The two groups exhibited significant well-marked cocaine-induced CPP in both 1-day (d = 1.38 and d = 1.11 at ps < .001 one-tailed in exercised and sedentary mice) and 21-day post-conditioning tests (d = 1.09 and d = 1.15 at ps < .001 one-tailed in exercised and sedentary mice). The (small) effects underlying interaction between housing and the drug treatment were not significant for 1-day (d = 0.19 at p = .48 two-tailed; 95% CI -0.35 to 0.73) or 21-day post-conditioning tests (d = 0.05 at p = .87 two-tailed; 95% CI -0.49 to 0.59). Conclusion. If physical exercise in rodents “truly” impacts CPP induced by drugs of abuse under comparable experimental parameters - as suggested by some studies (either positively or negatively) -, our results indicate that the size of such effects may be quite small, an information rarely reported in the literature.