TEMPORAL VARIATION IN THE INTERACTION BETWEEN CALCIUM-CHANNEL BLOCKERS AND MORPHINE-INDUCED ANALGESIA

Circadian variations in the interaction between calcium channel blocke rs and morphine-induced analgesia were determined by the mouse hot-pla te test. Calcium channel blockers diltiazem, verapamil, or nicardipine alone did not display any significant analgesic effect, but all of th em potentiated morphine-induced analgesia when injected 30 min prior t o morphine at most of the injection times. In terms of percent absolut e potentiation, they produced more potentiation during the light perio d than darkness. Their potentiating effects decreased abruptly during darkness, and around the midtime of the dark period no significant pot entiation of morphine-induced analgesia was observed. It is concluded that these fluctuations in the magnitude of interaction between calciu m channel blockers and morphine must be taken into consideration parti cularly in studies dealing with the role of calcium in analgesia.