Caffeine enhances the stimulant effect of methamphetamine, but may not affect induction of methamphetamine sensitization of ambulation in mice.

Methamphetamine (MAP: 1 and 2 mg/kg SC) and caffeine (CAF: 1, 3, 10 and 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to 4-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeatedly receiving CAF showed no significant change in the sensitivity to MAP. Combined administration of MAP with CAF increased the effect. In the combinations of MAP (1 mg/kg) with CAF (3, 10 and 30 mg/kg), and MAP (2 mg/kg) with CAF (1 and 3 mg/kg), the effect was enhanced by the repeated administration. However, MAP sensitization was not modified by the combination with CAF in the repeated administration schedule, except in the combination of MAP (1 mg/kg) with CAF (30 mg/kg). The ambulation-increasing effects of MAP (1 mg/kg), CAF (10 mg/kg) and combination of MAP with CAF were almost equivalently inhibited by SCH 23390 (0.01 and 0.1 mg/kg SC) and YM-09151-2 (0.01 and 0.1 mg/kg SC). However, the inhibitory effects of apomorphine (0.05 mg/kg SC) and N6-(L-phenylisopropyl)-adenosine (0.1 and 0.2 mg/kg SC) were stronger for CAF than for MAP and the combination, and those of alpha-methyl-p-tyrosine (200 mg/kg IP, 4 h before) and reserpine (1 mg/kg SC, 4 h before) were stronger for MAP and CAF alone than for the combination. The present results suggest that, although the combination of MAP and CAF enhances the ambulation-increasing effect through an interaction at dopaminergic system, CAF may not significantly modify the induction of MAP sensitization in mice.