Sleep-promoting action of excitatory amino acid antagonists: a different role for thalamic NMDA and non-NMDA receptors.

Changes in the sleep-waking cycle of freely moving cats were studied during application of excitatory amino acid antagonists in the ventro-posterolateral thalamic nuclei by microdialysis. DL-2-Amino-5-phosphono-pentanoic acid (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, produced an increase in the deep stages of slow wave sleep and in paradoxical sleep and a decrease in the light stages of slow wave sleep (SWS1), while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), at a concentration selective for the non-NMDA receptors, produced a marked increase in SWS1. These results indicate a strong sleep-promoting action of excitatory amino acid antagonists and suggest that thalamic NMDA and non-NMDA receptors may play different roles in sleep regulation. Thus, changes in the sleep-waking cycle should be carefully evaluated when assessing the potential clinical use of excitatory amino acid antagonists.