Interaction between caffeine and methamphetamine by means of ambulatory activity in mice

Effects of repeated administration of caffeine as well as interaction between caffeine and methamphetamine were investigated by means of ambulatory activity in mice. The single administration of caffeine increased the ambulatory activity at 10 and 30 mg/kg, sc, but scarcely increased at 3 mg/kg and at 100 mg/kg which is a subconvulsive dose. Methamphetamine 2 mg/kg, sc also increased the ambulatory activity. The combined administration of caffeine (1-100 mg/kg) and methamphetamine (2 mg/kg) showed a synergistic action as compared with the effects of the individual drugs. The repeated 5-times administration of caffeine (10, 30, and 100 mg/kg) at intervals of 3-4 days produced neither tolerance nor reverse tolerance to caffeine. The caffeine-experienced mice showed no marked change in the sensitivity to the ambulation-increasing effect of methamphetamine 2 mg/kg. In contrast, the repeated administration of methamphetamine 2 mg/kg induced not only reverse tolerance to methamphetamine itself but also cross reverse tolerance to caffeine (30 mg/kg). Furthermore, the methamphetamine-experienced mice also showed an increased activity after challenge administration of saline. The present results suggest that, although caffeine showed central stimulant effect, the characteristics are different from those of methamphetamine.