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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.

Rauhut, Anthony S., Justina A. Warnick, and Abigail L. Stasior. Differential Effects of Voluntary Exercise on Development and Expression of Methamphetamine Conditioned Hyperactivity and Sensitization in Mice. Pharmacology, Biochemistry and Behavior 193 (2020): e172934. https://www.sciencedirect.com/science/article/pii/S0091305719304009#!

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