Modification of Morphine-Induced Analgesia, Tolerance and Dependence by Bromocriptine

The effect of small doses of bromocriptine, a dopamine agonist, on morphine-induced analgesia, tolerance and dependence was investigated in mice. Bromocriptine at dose of 0.04 and 0.08 mg/Kg did not affect the base line of tail flick latency of mice but dose-dependently potentiated the morphine analgesia. Pretreatment of mice with 5 mg/Kg of sulpiride, a D-2 antagonist, not only blocked the effect of 0.08 mg/Kg of bromocriptine but also antagonized the morphine analgesia. Daily injections of 10 mg/Kg of morphine rapidly developed tolerance to the analgesic effect in control animals. Daily combined treatment of bromocriptine with morphine supperssed the development of tolerance to morphine suppressed the development of tolerance to morphine analgesia in a dose-dependent manner. However, in the animals daily treated with bromocriptine (0.08 mg/Kg) plus sulpiride (5 mg/Kg), the development of tolerance to the morphine analgesia was not significantly modified. Acute dependence was induced by administration of 100 mg/Kg of morphine. Administration of bromocriptine 30 min before naloxone significantly decreased the naloxone ED50 for inducing jumping in mice. Coadministration of sulpiride with bromocriptine to potentiate the withdrawal syndrome of morphine dependence.