NMDAR activation regulates the daily rhythms of sleep and mood
| Autor: | Roger A. Kroes, Laurits Sørensen, Jeffrey Burgdorf, M. Amin Khan, Martha Hotz Vitaterna, Fred W. Turek, Torsten M. Madsen, Eun Joo Song, Christopher Olker, Joseph R. Moskal, Edward P Christian |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty ketamine media_common.quotation_subject Basic Science of Sleep and Circadian Rhythms Audiology Electroencephalography NMDA receptors Receptors N-Methyl-D-Aspartate Non-rapid eye movement sleep Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Rhythm Physiology (medical) medicine Animals Spiro Compounds EEG sleep Wakefulness 030304 developmental biology media_common 0303 health sciences medicine.diagnostic_test business.industry sleep deprivation Circadian Rhythm Rats ultrasonic vocalizations Affect Sleep deprivation Mood Facilitation NMDA receptor Neurology (clinical) medicine.symptom business psychological phenomena and processes 030217 neurology & neurosurgery Vigilance (psychology) |
| Zdroj: | Sleep |
| ISSN: | 1550-9109 0161-8105 |
| DOI: | 10.1093/sleep/zsz135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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