[Naloxone-resistant EEG slowing induced by the synthetic opioid peptide FK 33-824 in the 4th cerebral ventricle of the dog].
In order to determine the importance of opioid peptides in the central control of wakefulness, the synthetic analogue of Met-Enkephalin, FK 33-824 (d-Ala-2-Phe-Met-(O)-ol-Enkephalin) which is more resistant to enzymatic degradation, was perfused in increasing concentrations (20, 100, 200, and 400 micgrograms/ml) through the fourth cerebral ventricle of the conscious dog. In the EEG (Power-spectral density in continuous acquisition) high concentrations (200--400 micgrograms/ml) induce slowing (theta--delta) with overlying beta-activity. This was reflected in the animals behaviour resulting in a sleep-like state which in spite of the administration of high doses of the antagonist Naloxone (100 micrograms/kg i.v.) sustained for 12 hours. A simultaneously dose-related respiratory depression (drop in arterial pO2 and an increase in arterial pCO2) was reversed by Naloxone. It is concluded that the opioid peptide FK 33-824 induces EEG-slowing which is mediated by a subpopulation of opiate-binding sites, possibly the kappa-receptors. These receptors are different from binding sites mediating respiratory depression (micro-receptors) as they interact with the opiate-antagonist Naloxone.