Influence of Ionotropic Glutamate Receptor Channel Blockers on the Effects of Sleep Deprivation in Rats

Abstract

Experiments on Krushinskii–Molodkina rats, with an inherited predisposition to audiogenic convulsions, and Wistar rats, which are resistant to the convulsion-inducing effects of sound, were performed to study the influence of selective noncompetitive NMDA glutamate receptor blockers (memantine and IEM-1921) and mixed-type antagonists acting on both NMDA and Ca-permeable AMPA-kainate receptors (IEM-1754 and IEM-1925) on the effects of sleep deprivation. These studies showed that the actions of these ionotropic glutamate receptor channel blockers on the effects of sleep deprivation in rats of both strains were similar, despite the differences in their predispositions to audiogenic seizures. During the first three hours after administration of memantine and IEM-1921 on the background of prior sleep deprivation, increases in the total duration of waking were seen, with a significant decrease in the proportion of slow-wave sleep and almost complete blockade of REM (paradoxical) sleep. These effects were probably due to blockade of NMDA receptors in the functional systems of the brain regulating the duration and depth of slow-wave sleep and responsible for triggering and maintaining REM sleep. During the first three hours after administration of the nonselective dicationic glutamate receptor antagonists (IEM-1754 and IEM-1925) on the background of sleep deprivation, their blocking actions on REM sleep were significantly decreased. During the second 3-h period after sleep deprivation in control experiments and after treatment with all glutamate receptors other than memantine, there were significant increases in the total duration of REM sleep, i.e., a rebound phenomenon was seen. The blocking action of memantine on the system triggering and maintaining REM sleep lasted about 6 h, after which the rebound phenomenon was also seen. Overall, memantine produced more marked and longer-lasting changes in the organization of sleep than the other glutamate receptor antagonists studied.