Development and persistence of methamphetamine-conditioned hyperactivity in Swiss-Webster mice.

These experiments examined the development and persistence of methamphetamine-conditioned hyperactivity in Swiss-Webster mice. Experiments 1 and 2 examined the development of conditioned hyperactivity, varying the methamphetamine dose (0.25-2.0 mg/kg), the temporal injection parameters (continuous; experiment 1 or intermittent; experiment 2), and the comparison control group (saline; experiment 1 or unpaired; experiment 2). Experiment 3 examined the persistence of methamphetamine-conditioned hyperactivity by comparing mice 1 (immediate) or 28 (delay) days after drug withdrawal. In each experiment, several behavioral measures (vertical counts, distance traveled, and velocity) were recorded and temporal analyses conducted to assess methamphetamine-conditioned hyperactivity. In experiments 1 and 2, it was found that methamphetamine-conditioned hyperactivity was (i) dose-dependent, (ii) detected early in the session, and (iii) detected by a behavioral measure indicative of general activity (i.e. distance traveled), and (iv) varied as a function of the number of conditioning sessions. In experiment 3, it was found that conditioned hyperactivity persisted for 28 days, though was weakened by nonassociative factors, following methamphetamine withdrawal. Collectively, these results suggest that conditioned hyperactivity to methamphetamine is robust and persists after prolonged periods of drug withdrawal in mice. Furthermore, these results are consistent with an excitatory classical conditioning interpretation of conditioned hyperactivity.