EEG-BEHAVIORAL DISSOCIATION AFTER MORPHINE-LIKE AND CYCLAZOCINE-LIKE DRUGS IN THE DOG - FURTHER EVIDENCE FOR 2 OPIATE RECEPTORS

Previous studies have suggested the presence of multiple opioid receptors. In the chronic spinal dog, the .mu. receptor was postulated to mediate behavioral indifference, whereas the .kappa. receptor was associated with sedation. The effects of morphine, a .mu. agonist, were compared with those of Win 35,197-2 (ethylketocyclazocine) and ketocyclazocine, .kappa. agonists, in the unrestrained intact dog. Intravenous administration of morphine (0.5, 1.0 and 2.0 mg/kg), Win 35,197-2 (0.05, 0.1 and 0.2 mg/kg), and ketocyclazocine (1.6 mg/kg) caused similar dissociation of the EEG and behavior. The dissociation was characterized by high voltage delta EEG synchrony primarily in the parietal cortex which accompanied ataxia and catalepsy in nonsleeping postures. Morphine increased total sleep and slow wave sleep, and lowered temperature and heart and respiratory rates. The .kappa. agonists did not increase total sleep but increased temperature and heart and respiratory rates. Vomiting occurred more often after morphine than after the .kappa. agonists. In certain instances, the effects of morphine were completely antagonized by a low dose of naloxone (30 .mu.g/kg), whereas 33 times the dose (1 mg/kg) was required to antagonize the effects of Win 35,197-2. The disparate effects of the .mu. and .kappa. opioid agonists on behavior, sleep and the EEG and their differences in sensitivity to naloxone antagonism evidently extend and support the concept of multiple opiate receptors in the brain. The sedative effects of the opioids are apparently mediated at the .mu. receptor.