Behavioral effects of naloxone and nalorphine preceding and following morphine maintenance in the rhesus monkey

The effects of morphine, naloxone, and nalorphine on responding maintained under a variable-interval schedule of food presentation were assessed in rhesus monkeys before and after successive periods of daily morphine maintenance (15.0 mg/kg/day SC). Withdrawal from morphine dependence was accomplished gradually following the first two maintenance periods and abruptly following the third period. Schedule-controlled responding was disrupted when morphine maintenance was abruptly discontinued but not when the maintenance dosage was gradually reduced to zero. Tolerance to the acute effects of IV morphine on responding developed during morphine maintenance and dissipated after daily injections were discontinued. The effects of IV naloxone and IV nalorphine following each period of morphine maintenance were generally similar to their effects in initial determinations. These data indicate that tolerance-producing regimens of repeated daily injections with morphine do not necessarily produce enduring changes in the effects of opiate antagonists on schedule-controlled behavior. Additionally, gradual withdrawal from morphine maintenance can minimize the behavioral disruptions that attend abrupt abstinence.