Chronic forced exercise during adolescence decreases cocaine conditioned place preference in Lewis rats

Abstract

Chronic physical activity (exercise) may be beneficial in the prevention of substance use disorders; however, the extent to which physical activity can interfere with the reinforcing effects of drugs during the adolescent period, which is one of great vulnerability for drug experimentation, has not been fully evaluated. Here, we assess the effects of chronic forced exercise during adolescence on preference for cocaine using the conditioned place preference (CPP) paradigm in male and female Lewis rats. The group of rats exposed to exercise ran on a treadmill for 6 weeks on a progressive time-increased schedule for up to 1h of exercise per day, while the groups of sedentary rats remained in their home cage. Following the 6 weeks of exercise exposure, rats were tested for cocaine CPP. Results showed that chronic exercise significantly attenuated cocaine CPP in both males and females compared to a sedentary environment. Furthermore, male exercise rats failed to show significant cocaine CPP. In contrast, female exercise rats still showed cocaine CPP but it was significantly reduced compared to the female sedentary rats. Females also exhibited greater cocaine CPP than males overall. These findings suggest that strategies to promote physical activity during adolescence may be protective against cocaine abuse in both males and females, and these findings merit further investigation. We also corroborate a gender-specific sensitivity to the reinforcing effects of cocaine, highlighting the need to consider gender-tailored exercise interventions for drug abuse prevention.

Fig. 1

Forced exercise and conditioned place preference timeline. Chronic forced exercise (treadmill running) began 6 weeks prior to a classic conditioned place preference test for cocaine. Exercise was continued throughout the CPP paradigm, as well as after the final CPP test, until all rats were sacrificed.

Fig. 2

Mean change in time spent in cocaine-paired box before and after conditioning. Sedentary males, sedentary females, and exercise females showed a significant CPP for cocaine (*p < 0.001); however, exercise males did not. Exercise attenuated cocaine preference in both sexes (p = 0.05), and females exhibited a greater cocaine CPP than males (p = 0.001).

Fig. 3

Locomotor activity during cocaine CPP conditioning. Male rats were more active than female rats (p < 0.001), and rats were more active on cocaine than saline (p < 0.001). (A) Mean locomotor activity over the 4 days on which cocaine was administered. (B) Mean locomotor activity over the 4 days on which saline was administered.

Fig. 4

Mean body weight for each of the four groups of rats over the course of the study. All groups gained a significant amount of weight over the study (p < 0.05). Male rats weighed significantly more than females (p < 0.05).

Fig. 5

Mean daily food intake for each of the four groups for each week. There was a steady increase in food intake between weeks 1 and 5 exhibited by males (p < 0.05); however, female food intake was more erratic weekly. Male rats consumed significantly more food than female rats (p < 0.05).