CAFFEINE ENHANCES ACUTE STIMULANT EFFECT OF MORPHINE BUT INHIBITS MORPHINE SENSITIZATION WHEN ASSESSED BY AMBULATION OF MICE

1. The repeated administration of single dose of morphine (10 mg/kg) a t 3 to 4 day-intervals caused sensitization to its ambulation-increasi ng effect. 2. The same treatment with caffeine (1, 3 and 10 mg/kg) did not change the effect of caffeine itself, but tended to reduce the se nsitivity to morphine. 3. Combination of morphine with caffeine enhanc ed the effect in the 1st administration, though the mice given such co mbination showed almost the same activity during the repeated adminisr tation, and the sensitivity similar to the saline control or drug-naiv e mice to challenge morphine. 4. The ambulation increases caused by mo rphine (10 mg/kg), caffeine (10 mg/kg) and their combination were redu ced by SCH 23390 (0.01 mg/kg), YM-09151-2 (0.01 mg/kg), reserpine (1 m g/kg), alpha-methyl-p-tyrosine (200 mg/kg), naloxone (1 mg/kg) and N-6 -(L-phenylisopropyl)-adenosine (0.2 mg/kg), although the inhibitory ac tions were different dependent on the drug conditions. 5. The present results indicate complex interactions between morphine and caffeine; e nhancement of the acute stimulant effect by the combined administratio n, but inhibiton of morphine sensitization by caffeine, probably throu gh dopaminergic, opioid and adenosinergic systems.