Electroencephalographic and behavioral effects of D-ala2-methionine-enkephalinamide and morphine in the rat

Rats were prepared with chronic cortical and temporalis muscle electrodes and bilateral intraventricular (i.vt.) cannulae. The direct and voltage integrated electroencephalogram (EEG) and integrated electromyogram as well as gross behavior were monitored after the i.vt. injection of D-enkephalin (10--240 microgram), morphine (2.5--40 microgram), naloxone (25--50 microgram) or sterile water (10 microliter). EEG high-amplitude slow-frequency waves (EEG slow bursts) occurred after i.vt. morphine or D-enkephalin and were associated with behavioral stupor. The behavioral depressant effect was followed by behavioral arousal and EEG activation. The EEG voltage output during morphine or D-enkephalin-induced EEG slow-wave activity was dose-dependent and was correlated with the behavioral state of the rat. D-Enkephalin was less potent and shorter-acting than morphine but produced a greater maximal response with respect to increasing the EEG voltage output. The effects of D-enkephalin and morphine were antagonized by pretreatment with naloxone (10 mg/kg s.c.). On the other hand, the i.vt. injection of naloxone alone or sterile water had no disruptive effect of the EEG or behavior of the rat. The results of this study established a dose-response relationship for the i.vt. administration of morphine and D-enkephalin using the direct and voltage integrated EEG. The demonstrated difference in maximal EEG response between morphine and D-enkephalin supports the contention that heterogenous opiate receptors in the brain may mediate their effects.