Effects of morphine pretreatment on cocaine cardiotoxicity in anesthetized guinea-pigs

Cardiovascular and lethal effects of intravenous cocaine infusion were compared in guinea-pigs pretreated chronically with morphine or saline. Alzet minipumps filled with either morphine solution (30 micrograms/kg/hr for 6 days) or isotonic saline were implanted subcutaneously in animals 6 days before cocaine infusion. On the morning of the 7th day, animals were anesthetized with urethane (1000 mg/kg i.p.) and an i.v. infusion of cocaine was begun at a rate of 1.9 mg/kg/min. All animals were spontaneously breathing room air throughout the experiments. Death occurred by respiratory arrest in all animals; however, there was a significant decrease in the time to respiratory arrest in the morphine-pretreated guinea-pigs. All animals showed a gradual increase in the atrio-ventricular conduction interval (PR-interval) and in mean arterial pressure up until the time that respiration ceased. There were no disturbances in cardiac rhythm before respiratory arrest. This suggests that the predominant cardiovascular and lethal effects of cocaine in urethane-anesthetized guinea-pigs are the result of its local anesthetic (membrane stabilizing) action, and that morphine potentiates this effect of cocaine, but does not alter the pattern of cocaine toxicity.