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

Abstract

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 coadministration 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.