Blockade of the discriminative effects of morphine in the rat by naltrexone and naloxone

The capacity of the specific narcotic antagonists naltrexone and naloxone to block the discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete-trial avoidance task. The antagonists produced a dose-dependent and time-dependent blockade of morphine's effects as measured by responding on the morphine-appropriate choice lever. Naltrexone and naloxone were equipotent when given subcutaneously concomitantly with subcutaneously administered morphine. However, when the antagonists were administered orally at 0, 2, 4 or 8 h prior to s.c. morphine, naltrexone was more potent that naloxone at every time point and had a duration of action at least twice that of oral naloxone. The discriminitive effects of the narcotic analgesics morphine and methadone were also compared after oral and subcutaneous administration. Both drugs produced dose-related discriminative effects and were one-tenth as potent by the oral as by the subcutaneous route of administration. These results suggest that the discriminative effects produced by morphine in the rat can provide an animal model for the quantitative evaluation of the narcotic antagonist properties of drugs that might be considered for use in narcotic antagonist maintenance programs for the treatment of narcotic addiction.Predoctoral trainee of the Public Health Service Graduate Pharmacology Training Grant 2T1 GM179. This project represents partial fulfillment of the degree of Doctor of Philosophy at Emory UniversityRecipient of Research Scientist Development Award K02 DA00008