Reverse-tolerance phenomenon in methamphetamine induced behavioral stereotypy and impairment of cliff avoidance reaction after subchronic methamphetamine administration in rats

Clinical evidence of methamphetamine (MAP)-induced reverse-tolerance phenomenon is available in studies of methamphetamine psychosis. To examine the clinical relevance of the reverse tolerance phenomenon as a model of this psychosis, two experiments were conducted using rats. In the first experiment, we examined the relationship of MAP (4 mg/kg/day)-induced reverse tolerance in behavioral stereotypy to impairment of the cliff avoidance reaction (CAR). The stereotypy scores by the method of Creese and Iversen reached a maximum at day 14, and were unchanged thereafter. Impairment of CAR appeared in 3 of 6 rats at day 21 or 28 without motor ataxia, as rated by the scoring system of Hiramatsu et al. This suggested that cognitive dysfunction reflected by CAR impairment may develop after MAP-induced reverse-tolerance phenomenon, as evaluated by the behavioral stereotypy rating scale. In the second experiment, the effect of PCP (1 mg/kg) on CAR was examined in rats pretreated with MAP (4 mg/kg/day) for 30 days. No behavioral stereotypy or CAR impairment was found in these rats for 1 hour after PCP challenge. This showed that MAP-induced reverse-tolerance did not alter sensitivity to PCP in producing behavioral stereotypy or CAR impairment.