INTERACTIONS OF OPIOIDS WITH CAFFEINE - EVALUATION BY AMBULATORY ACTIVITY IN MICE

Morphine (up to 10 mg kg(-1)), buprenorphine (up to 0.1 mg kg(-1)), pe ntazocine (30 mg kg(-1)) and caffeine (up to 10 mg kg(-1)), significan tly increased mouse ambulation. The combination of morphine, buprenorp hine and pentazocine with caffeine generally enhanced the effect. Dopa mine D-1- and D-2-receptor bockade, depletion of stored dopamine, and inhibition of dopamine synthesis could reduce the ambulation increased by single administration of morphine, buprenorphine and caffeine, and by combined administration of morphine and buprenorphine with caffein e. Although naloxone (0.1-3 mg kg(-1)) itself did not change mouse amb ulation, at 3 mg kg(-1), it reduced the effect of caffeine. The repeat ed administration of morphine (10 mg kg(-1)) induced a sensitization t o the ambulation-increasing effect, and was inhibited by the combinati on of caffeine (10 mg kg(-1)) in the repeated administration schedule. The repeated administration of caffeine (10 mg kg(-1)) with buprenorp hine (0.3 mg kg(-1)) resulted in a decrease in the effect to the level of caffeine alone. The development of cross-sensitization to morphine (10 mg kg(-1)) by the repeated treatment with buprenorphine (0.3 mg k g(-1)) was inhibited by caffeine (10 mg kg(-1)). Our results suggest t hat the dopaminergic systems are involved in the enhanced interaction of opioids having agonistic action on mu- or sigma- receptors with caf feine. However, it is also considered that, following the repeated adm inistration, caffeine acts to reduce the sensitivity to the ambulation -increasing effect of opioids, probably inducing up-regulation of aden osinergic systems.