Perfusion of the fourth cerebral ventricle with fentanyl induces naloxone-reversible bradycardia, hypotension, and EEG synchronisation in conscious dogs

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Abstract
Injection of fentanyl into the cisterna magna of the brain leads to hypotension and bradycardia in anesthetised dogs. To determine if this effect is related to the recently discovered opiate receptors fentanyl was perfused in increasing concentrations (2.5–20 μg/ml) through the cerebro-ventricular system in conscious dogs. Blood pressure was recorded continuously from a punctured exteriorised carotid artery; heart rate was derived from the ECG. Baroreflex activity was tested repeatedly by clamping of both common carotid arteries. Cerebral activity was evaluated from the EEG. Perfusion of the fourth cerebral ventricle resulted in a concentration-related fall in heart rate by 43% and in an inhibition of the reflex response of heart rate to carotid clamping. In contrast, blood pressure fell only moderately by 14% and its reflex response was well maintained. The EEG pattern changed from frequencies in the beta-band (awake control) to gradual synchronisation with delta-activity corresponding to behavioural signs of tranquillisation and sleep-like states. All these effects were reversed by naloxone. No effects were seen when fentanyl was perfused through the lateral ventricles and third ventricle although this yielded similar serum concentration as after perfusion of the fourth ventricle. It is concluded that opiate receptors bordering the fourth cerebral ventricle mediate the cardiovascular and hypnotic action of fentanyl.