REDUCTION OF MORPHINE-DEPENDENCE AND POTENTIATION OF ANALGESIA BY CHRONIC COADMINISTRATION OF NIFEDIPINE

Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia mea sured in the hot-plate, but not in the tail-flick test. Further experi ments were carried out using the hot-plate test only. Pretreatment wit h nifedipine partially restores the analgesic action of morphine in mo rphine-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 preven t the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-indu ced withdrawal syndrome (quantified by counting head shakes) in the te st carried out 24 h after the injection of nifedipine, when the drug d id not affect morphine analgesia. Chronic treatment with either morphi ne or nifedipine did not produce a significant increase in the density of [H-3] naloxone or [H-3] prazosin binding sites in the cortex and i n the rest of the brain (measured 24 h after the last dose), but the c ombined treatment resulted in a significant increase in the cortical [ H-3] prazosin binding site density. The present results suggest that o piate tolerance and physical dependence may be separated by co-adminis tration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine dur ing chronic treatment and prevent development of abstinence.