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

Abstract

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.

Figure 1. Test for Conditioned Hyperactivity in Experiment 1

Distance travelled (cm) (upper panel) and the number of vertical counts (lower panel) on the test session. The symbols *, # and &denote significant differences between the low (0.5 mg/kg), moderate (1.0 mg/kg) and high (2.0 mg/kg) methamphetamine doses, respectively, and the vehicle control dose, p < 0.05.

Figure 2. Test for Conditioned Hyperactivity in Experiment 2

Distance travelled (cm) (upper panel) and the number of vertical counts (lower panel) on the test session. Thesymbol * denotes a significant difference between the moderate (1.0 mg/kg) methamphetamine dose and the unpaired control group, p < 0.05.

Figure 3. Test for Conditioned Hyperactivity in Experiment 3

Distance travelled (cm) (upper panels) and the number of vertical counts (lower panels) during the entire 30-minute session (right panels) or in 5-min bins (left panels) for mice tested 1 (Immediate) or 28 (Delay) days following drug withdrawal. The symbols * and #denote significant differences between the paired-immediate and paired-delay mice, respectively, and their unpaired counterparts, p < 0.05. The brackets denote a significant difference between immediate mice and their delay counterparts, p < 0.05.

Figure 4. Test for Methamphetamine Sensitization in Experiment 3

Distance travelled (cm) (upper panel) and the number of vertical counts (lower panel) for mice tested 1 (Immediate) or 28 (Delay) days following drug withdrawal. The symbols *and #denote significant differences between the paired-immediate and paired-delay mice, respectively, and their unpaired counterparts, p < 0.05.