NMDAR activation regulates the daily rhythms of sleep and mood

Jeffrey S. Burgdorf*, Martha H. Vitaterna, Christopher J. Olker, Eun Joo Song, Edward P. Christian, Laurits Sørensen, Fred W. Turek, Torsten M. Madsen, M. Amin Khan, Roger A. Kroes, Joseph R. Moskal

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Study Objectives: The present studies examine the effects of NMDAR activation by NYX-2925 diurnal rhythmicity of both sleep and wake as well as emotion. Methods: Twenty-four-hour sleep EEG recordings were obtained in sleep-deprived and non-sleep-deprived rats. In addition, the day-night cycle of both activity and mood was measured using home cage ultrasonic-vocalization recordings. Results: NYX-2925 significantly facilitated non-REM (NREM) sleep during the lights-on (sleep) period, and this effect persisted for 3 days following a single dose in sleep-deprived rats. Sleep-bout duration and REM latencies were increased without affecting total REM sleep, suggesting better sleep quality. In addition, delta power during wake was decreased, suggesting less drowsiness. NYX-2925 also rescued learning and memory deficits induced by sleep deprivation, measured using an NMDAR-dependent learning task. Additionally, NYX-2925 increased positive affect and decreased negative affect, primarily by facilitating the transitions from sleep to rough-and-tumble play and back to sleep. In contrast to NYX-2925, the NMDAR antagonist ketamine acutely (1-4 hours post-dosing) suppressed REM and non-REM sleep, increased delta power during wake, and blunted the amplitude of the sleep-wake activity rhythm. Discussion: These data suggest that NYX-2925 could enhance behavioral plasticity via improved sleep quality as well as vigilance during wake. As such, the facilitation of sleep by NYX-2925 has the potential to both reduce symptom burden on neurological and psychiatric disorders as well as serve as a biomarker for drug effects through restoration of sleep architecture.

Original languageEnglish (US)
Article numberzsz135
JournalSleep
Volume42
Issue number10
DOIs
StatePublished - Oct 1 2019

Keywords

  • EEG
  • Ketamine
  • NMDA receptors
  • Sleep
  • Sleep deprivation
  • Ultrasonic vocalizations

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)

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    Burgdorf, J. S., Vitaterna, M. H., Olker, C. J., Song, E. J., Christian, E. P., Sørensen, L., Turek, F. W., Madsen, T. M., Khan, M. A., Kroes, R. A., & Moskal, J. R. (2019). NMDAR activation regulates the daily rhythms of sleep and mood. Sleep, 42(10), [zsz135]. https://doi.org/10.1093/sleep/zsz135