[The enkephalinase mechanisms of the resistance and tolerance to the analgesic effect of morphine in rats. Differences in the effects of naloxone in morphine-sensitive, morphine-resistant and morphine-tolerant rats].

In morphine-sensitive (s. c. 1.5 mg/kg) Wistar rats i.p. injection of 0.3 mg/kg naloxone either did not change nociception (tail-flick test) or induced hyperalgesia. In morphine-resistant rats 0.2-0.7 mg/kg naloxone injection induced analgetic effect but 1.0 mg/kg induced hyperalgesia. In morphine-sensitive rats chronic morphine administration induced the tolerance and naloxone injection evoked analgetic effect. Morphine inoculation just after naloxone analgesia was over induced analgetic effect. In morphine-resistant and -tolerant rats chronic naloxone administration induced gradual decrease and subsequent disappearance of its analgetic effect and subsequent morphine injections induced analgetic effect for some days. It is suggested that naloxone in morphine-resistant and -tolerant rats with high level of enkephalinase activity functions as its inhibitor. Chronic naloxone administration evoked progressive inhibition of enkephalinase activity that induced the morphine analgetic effect in morphine-resistant and -tolerant rats.