Fentanyl in the fourth cerebral ventricle causes respiratory depression in the anesthetized but not in the awake dog.

Specific binding sites for opiate-induced bradycardia, hypotension and EEG-synchronization are located in areas bordering the IVth cerebral ventricle in the dog. To see if the clinically observed opiate-induced respiratory depression is mediated selectively from ponto-bulbar respiratory neurones, increasing concentrations of fentanyl (2.5-5-10-20 micrograms/ml) were perfused through the IVth cerebral ventricle in canines. Contrary to the awake state, fentanyl-perfusion during halothane-anesthesia (0.75 vol%/O2) induced a dose-related increase in arterial PCO2. This effect was reversed by subsequent naloxone-perfusion (20 micrograms/ml). The administration of halothane alone over the same period of time did not affect PCO2 in a similar manner. It is suggested that higher cortical centers which are involved in sensory awareness may modulate respiratory neurones in the medulla, since the depression of these higher centers by halothane resulted in opiate-induced respiratory impairment. An additive effect of fentanyl- and halothane-induced release of opiate-like peptides (enkephalins) on respiration should also be considered.