Discharge patterns of bulbar respiratory neurons in response to the morphinomimetic agent, fentanyl, in chloralosed dogs

Abstract

In anaesthetized, paralysed and artificially ventilated dogs, activities were recorded from the phrenic nerve and from respiratory units within the nucleus tractus solitarii (nTS), the nucleus ambiguus (nA) and the nucleus retroambigualis (nRA). The respiratory neurons were classified according to their discharge pattern and their response to lung inflation. Fentanyl injected into the vertebral artery (0.5–2 μg/kg) or intravenously (10 μg/kg) produced a depressant effect on the phrenic nerve motoneurons, on inspiratory cells (Iα and Iβ) and on phase-spanning expiratory-inspiratory neurons of the nTS and the nA. The duration of the inspiratory burst increased and the number of spikes and the peak activity were reduced. This pattern of inhibition was followed by complete blockade of spike genesis. Fentanyl also altered expiratory neurons: the duration of the expiratory discharge was enhanced. An increase followed by a decrease in the number of spikes per burst and a reduction in the peak acticity were observed. When the phrenic nerve was silent, continuous discharges appeared. High doses of fentanyl were needed to inhibit these tonic discharges. This pattern of inhibition concerns late peak expiratory units, expiratory units with a constant discharge pattern and the phase-spanning inspiratory-expiratory neurons. Naloxone antagonized these effects but induced the appearance of tonic discharges in fentanyl-treated phase-spanning expiratory-inspiratory neurons. Stimulation of peripheral chemoreceptors with almitrine (0.2 mg/kg i.v.) antagonized the effects of fentanyl. In addition, fentanyl facilitated the lung inflation reflex on respiratory neurons. In conclusion, fentanyl induces respiratory depression through a preferential effect on inspiratory neurons and alters the active inhibitory phase-switching mechanisms maintaining the expiratory periodicity. These experiments support the concept of an inhibitory influence of inspiratory neurons on expiratory cells and also support the idea that respiratory periodicity arises on a background of tonic activity for both inspiratory and expiratory neurons.