Behavioral effects of morphine and naloxone following chronic morphine administration.

The effects of morphine, naloxone, and combinations of these drugs were examined in squirrel monkeys under shock-postponement schedules. In the absence of a lever press, shocks could be presented every 4s. and each response postponed shock for 20s. Acutely, morphine (0.10-3.00 mg/kg) produced not only overall response-rate decreases, but also increases in the number of shocks, whereas naloxone (0.10-30.00 mg/kg) had little effect on responding. When given in combination with morphine, several doses of naloxone antagonized the rate-reducing and shock-increasing effects of morphine. Daily administration of morphine resulted in a substantial decrease in the number of shocks received and a moderate attenuation of the rate-decreasing effects of morphine (tolerance). Lower doses substituted for the fixed daily dose resulted in a smaller effect on behavior than under acute administration. Naloxone given in combination with the daily morphine dose or substitute for the daily morphine dose or substituted for the daily administration or morphine, produced effects similar to those seen prior to chronic drugging. Thus, behavioural effects of naloxone were not altered even though tolerance to morphine was observed. Larger doses of naloxone continued to antagonize the effects of morphine for at least 24 h. No signs of physical dependence were noted when naloxone was administered or when administration of morphine ended.