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 heart-rate 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 saline 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 nalorphine-- or naloxone--induced withdrawal syndrome can either suppress, enhance or maintain behavior depending on the schedule conditions.