Methamphetamine-induced hyperactivity and reinforcement learning in rats selectively bred for high and low voluntary running

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The goal of the present research was to assess two lines of Wistar rats selectively bred for high (HVR) and low (LVR) voluntary wheel running, in comparison to a line of control (WT) rats. As previous research has outlined the benefits of voluntary exercise on substance abuse, this study investigated the role of possible genetic differences between rat lines on sensitivity to methamphetamine (Experiment 1), motivation to work for and self-administer methamphetamine (Experiment 2a), and learning to press a lever for a food reward (Experiment 2b). Experiment 1 investigated sensitivity to methamphetamine in HVR, LVR, and WT rats by comparing locomotor behavior after methamphetamine administration. Experiment 1 found that both HVR and LVR rats were less sensitive to the locomotor activating properties of methamphetamine compared to WT rats. Experiment 2a and 2b investigated learning to press a lever for a food pellet or an infusion of methamphetamine in HVR, LVR, and WT rats. Experiment 2a found that both HVR and LVR rats were less sensitive to the reinforcing properties of methamphetamine compared to WT rats, evidenced by their reduced lever pressing behavior. Experiment 2b found that HVR rats pressed a lever less for a food pellet compared to both LVR and WT rats, suggesting that HVR rats alone may value a food pellet as a behavioral reinforcer less than the other two rat lines. The results of this preliminary investigation suggest that exercise may be both necessary and sufficient to produce effects on drug use behaviors. One's (genetic) predisposition to engage in exercise may be independent of one's ability to benefit from exercise.