Respiratory Effects of the N-methyl-D-aspartate (NMDA) Antagonist, MK-801, in Intact and Vagotomized Chronic Cats

The effects on respiration of MK-801, an N-methyl-D-aspartate (NMDA) non-competitive antagonist, were studied in awake chronic cats by means of the plethysmographic technique. MK-801 (0.01-3.0 mg/kg) was first given i.v. in cumulative doses. The protocol was repeated 10-15 days later in the same animals after bilateral vagotomy. MK-801 selectively increased the duration of inspiration, causing an apneustic respiration but had no effect on the duration of expiration. The maximal inspiratory duration brought about by MK-801 in the intact cat (4.3 s; control 0.9 s) increased 4-fold after bilateral vagotomy (16.4 s; control 1.7 s). Such results suggest that the termination of the inspiratory phase in normal awake cats results from an interaction of pulmonary vagal afferent inputs (inactive on NMDA receptors) with a central mechanism in which NMDA-type glutamate receptors are activated by dicarboxylic amino acid neurotransmission.