COMPARISON OF ACUTE AND CHRONIC EFFECTS OF NIFEDIPINE ON NALOXONE-PRECIPITATED MORPHINE WITHDRAWAL IN MICE

Mice were rendered tolerant and dependent to morphine by subcutaneous injection of morphine over a period of 5 days. The effects of acute and chronic administration of dihydropyridine calcium channel antagonist nifedipine on the development of tolerance and naloxone-precipitated morphine withdrawal signs were investigated. A single injection of nifedipine proved to be effective in inhibiting some signs of morphine withdrawal but ineffective in blocking the development of tolerance to the ataxic action of morphine. The concurrent injections of nifedipine with morphine prevented most signs of morphine withdrawal but failed to have any effects on the development of tolerance to the ataxic action of morphine. The results suggest that alterations in dihydropyridine-sensitive calcium channels may be involved in the adaptations that occur on chronic treatment with morphine. It is also possible to conclude that separate mechanisms are involved in the development of tolerance and dependence.