Agonistic properties of narcotic analgesics and antagonists on the electroencephalogram and behavior in the rat and their reversal by naloxone

Adult female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes for recording of the electroencephalogram (EEG) and the electromyogram (EMG). Acute i.p. administration of the narcotic analgesics morphine, methadone, meperidine, or codeine was followed by the induction of high-voltage slow activity in the EEG during behavioral stupor of the rat, the duration of which was dose-related. Administration of the narcotic antagonists nalorphine, pentazocine, or cyclazocine resulted in similar EEG and behavioral changes. This initial period of EEG slow activity and behavioral stupor was uniformly succeeded by a secondary phase of EEG desynchrony and behavioral arousal, the duration of which depended upon the individual narcotic and antagonist agents. The narcotic antagonist naloxone, however, was devoid of such effects. Nalorphine administered at the dose ratios of 1:4 or 1:8 five min before morphine significantly reduced the duration of the morphine response. Administration of naloxone at a dose ratio of 1:5 five min before morphine, however, resulted in a complete reversal of the entire morphine effect. These results suggest that the induction of EEG slow activity in association with stuporous behavior of the rat is an agonistic property of narcotics and antagonist-analgesics which is reversed by “pure” narcotic antagonists.