Effects of intertrigeminal region NMDA and non-NMDA receptors on respiratory responses in rats

Respiratory disturbance, including apnea, can be induced by microinjection of glutamate into the intertrigeminal region (ITR) of the lateral pons, a region that is anatomically coupled to both the dorsal and ventral respiratory groups of the medulla. We showed that the ITR plays a functional role in regulating both vagal reflex apnea and spontaneous sleep-related apnea in rats, but the mechanisms have not been determined. This study shows that functional NMDA receptors are expressed in the ITR since the blockade of these receptors by AP5, a specific NMDA receptor antagonist, was fully effective in blocking apnea induced by glutamate injection within this region. Selective blockade of ITR NMDA receptors had no effect on the immediate apnea evoked by an intravenous 5-HT bolus, whereas the nonspecific glutamate receptor antagonist kynurenic acid significantly increased the duration of this vagal reflex apnea. These findings are of interest because pontine NMDA receptors participate in inspiratory off-switch mechanisms and have been implicated in various short- and long-term potentiation and depression phenomena. These data support the involvement of ITR non-NMDA receptors in modulation of reflex apnea per se, whereas NMDA receptors play a role in damping respiratory responses to transient disturbances.