Behavioral and pharmacokinetic interaction between morphine and haloperidol in the rat

Tail-flick latencies and morphine concentrations in the blood serum, brain (without striatum) and spinal cord were measured in rats receiving 10 mg/kg ip morphine with or without haloperidol pretreatment (0.1 or 1 mg/kg sc). Haloperidol pretreatment dose-dependently potentiated the analgesic action of morphine and interfered with tissue morphine levels. Morphine levels in the spinal cord were similar to those in the blood serum and were dose-dependently increased by haloperidol pretreatment; in the brain the appearance of morphine was delayed, the levels lower than in the blood serum, and the effect of both doses of haloperidol (augmentation of morphine level) was similar. The results indicate that the analgesic effect of morphine in the tail-flick test is correlated better with the spinal than cerebral morphine levels and that potentiation of morphine analgesia by haloperidol is due, at least in part, to pharmacokinetic interaction.