Involvement of NMDA receptors in inspiratory termination in rodents: effects of wakefulness

Abstract

We investigated the role of N-methyl-D-aspartate (NMDA) receptors in the off-switching of inspiration in rodents. Respiratory activity was measured by the plethysmographic method in Swiss and Balb c mice, Hartley guinea pigs, Wistar and Sprague-Dawley rats. The NMDA channel blocker dizocilpine (MK-801) administered systemically, had little effect on the timing of respiratory phases in intact animals. When dizocilpine was associated with a vagotomy performed under anesthesia, an apneustic respiratory pattern was obtained in all species and strains. As the anesthetic dissipated, the inspiratory pauses disappeared and the apneustic respiratory pattern was replaced by an eupneic respiratory pattern. Apneuses were re-instated by small doses of anesthetic (halothane, pentobarbital, alphaxolone-alphadolone or chloral hydrate) and suppressed by larger doses. We conclude that (i) the central NMDA-receptor dependent inspiratory off-switching mechanism previously described in cats and primates, also exists in rodents; (ii) wakefulness maintains a normal respiratory pattern after suppression of both the NMDA-receptor mediated and the vagally-mediated off-switching mechanisms; (iii) deep anesthesia suppresses inspiratory pauses in rodents.