Differential effects of voluntary exercise on development and expression of methamphetamine conditioned hyperactivity and sensitization in mice

Abstract

The present experiments determined the effects of voluntary home-cage wheel running on the development (Experiments 1 and 2a) and expression (Experiment 2b) of conditioned hyperactivity and long-term sensitization in male, Swiss-Webster mice. Mice experienced 3 weeks of wheel running (exercise) or not (sedentary) either beginning prior to (Experiments 1 and 2a), or immediately following (Experiment 2b), the acquisition phase. During the acquisition phase, mice (n = 12–15/group) received injections (subcutaneous) of either vehicle (saline) or methamphetamine (0.5 or 1.0 mg/kg, Experiment 1; 1.0 mg/kg, Experiments 2a and 2b) immediately prior to 5 locomotor-activity sessions. The extinction phase began 48 hours (h) (Experiment 1) or 3 weeks (Experiments 2a and 2b) after acquisition and all mice received vehicle injections prior to 4 locomotor-activity sessions. Tests of long-term sensitization occurred 72 h after the last extinction session and involved an escalating, methamphetamine-dose regimen (0.25 ➔ 1.0 mg/kg), 1 dose/session for 3 sessions. While pre-acquisition wheel running failed to alter development of conditioned hyperactivity after training with the 0.5 mg/kg methamphetamine dose, it blunted the development of conditioned hyperactivity, and blocked (Experiment 1) or attenuated (Experiment 2a) induction of long-term sensitization after training with the 1.0 mg/kg methamphetamine dose. Furthermore, while post-acquisition wheel running retarded extinction of conditioned hyperactivity, it did not alter expression of conditioned hyperactivity or long-term sensitization (Experiment 2b). Collectively, the results suggest that the impact of voluntary exercise on context-drug associations and long-term sensitization is critically dependent on the timing of exercise relative to drug conditioning.