Conditioned behavioral and physiological changes associated with injections of a narcotic antagonist in morphine-dependent monkeys

Environmental stimuli which are repeatedly associated with the nalorphine-induced withdrawal syndrome in morphine-dependent monkeys acquire the ability to produce a variety of conditioned behavioral and physiological responses. Morphine-dependent rhesus monkeys were studied under a fixed-ratio schedule where every tenth lever press produced a food pellet. After several pairings of a stimulus (light or tone) with intravenous injection of a dose of nalorphine which produced an immediate and severe withdrawal syndrome, onset of the stimulus alone produced conditioned suppression of lever pressing, heartrate decrease, vomiting and salivation. Conditioned suppression of responding and conditioned heart-rate changes persisted in post-dependent monkeys for one to four months after termination of chronic morphine treatment. No conditioned electrocardiogram, respiration or temperature changes were ever seen. A second group of morphine-dependent rhesus monkeys was studied under a schedule where every lever press produced an intravenous injection of morphine. After 10 pairings of a light with the intravenous injection of a dose of nalorphine which produced marked withdrawal signs and increased responding for morphine, presentation of the light and injection of sahne produced conditioned increases in responding for morphine. A third group of morphine-dependent rhesus monkeys was studied under a schedule where every nth lever press (n = 1 to 10) terminated a stimulus light associated with periodic injections of nalorphine or naloxone; lever-press responding was engendered and subsequently maintained. Thus, stimuli associated with the nalorphineor naloxone-induced withdrawal syndrome can either suppress, enhance or maintain behavior depending on the schedule conditions.