Opioid mechanisms of some behavioral effects of ketamine.

The effect of naloxone on the duration of sleep and on analgesia produced by ketamine, and on the development of tolerance and cross-tolerance with morphine to ketamine analgesic effects were investigated in mice. Ketamine produced a dose-dependent analgesia. Naloxone (4 mg/kg) significantly inhibited the analgesic effects of ketamine (40 mg/kg), but (given in a dose of 2 mg/kg) did not affect the duration of ketamine sleep. Chronic administration of ketamine (160 mg/kg twice daily for 7 days) resulted in a gradual shortening of ketamine sleep and in the development of tolerance to the analgesic action of ketamine. There also developed cross-tolerance between analgesic effects of morphine and ketamine. Ketamine (20 mg/kg) significantly inhibited symptoms of morphine abstinence produced in morphine-pelleted mice by naloxone administration or by pellet removal. The results suggest that at least some elements of the mechanism of action of ketamine and morphine may be common and related to the endogenous opioid system.