Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine.

Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co-administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co-administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence.