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 an d 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to mg/kg-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeat edly 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 M AP (2 mg/kg) with CAF (1 and 3 mg/kg), the effect was enhanced by the repeated administration. However, MAP sensitization was not modified b y the combination with CAF in the repeated administration schedule, ex cept in the combination of MAP (1 mg/kg) with CAF (30 mg/kg). The ambu lation-increasing effects of MAP (1 mg/kg), CAF (10 mg/kg) and combina tion 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 N-6-(L-phe nylisopropyl)-adenosine (0.1 and 0.2 mg/kg SC) were stronger for CAF t han for MAP and the combination, and those of alpha-methyl-p-tyrosine (200 mg/kg IF, 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 dopaminerg ic system, CAF may not significantly modify the induction of MAP sensi tization in mice.