Abstract

Repeated exposure to stimulant drugs such as cocaine makes animals more sensitive to their stimulant effects—a phenomenon that is known as ‘behavioural sensitization’. However, the magnitude of behavioural sensitization is not fixed but can vary according to life experiences and their interaction with biological factors. This thesis explores whether and how wheel running influences sensitization of the stimulant effects of cocaine as measured after repeated exposure to cocaine or to stress in the rat. Wheel running was chosen because of its natural variability among individuals and because it has been shown to act, at least in part, on the same neuronal substrate as drugs and stress. Three studies were conducted. In the first study we showed that engaging in high levels of wheel running activity protects against cocaine-induced behavioral sensitization. To demonstrate the generalizability of these findings, in the second study, using stress exposure instead of stimulant drugs to induce a sensitized behavioral response, we found that running also protects against stress-induced behavioral sensitization to cocaine and more so in animals that run the most. Finally, in the third study, we showed that engaging in high levels of wheel-running activity, after the fact, once a sensitized behavioral response to cocaine has already been established reverses this typically enduring phenomenon. The findings reported here reveal, for the first time, the regulatory effects wheel running can have on behavioral sensitization and highlight the importance of taking into account individual differences in running when studying the effects of this behavior. What is more, our behavioral model suggests running-mediated neuroplasticity within the neural circuitry involved in behavioral sensitization and may prove useful in studying the role of gene-environment interactions in experience-dependent neuroplastic changes.