The effects of diazepam on sleep depend on the photoperiod.

Acta Pharmacol Sin

Laboratory for Neurophysiology, Department of Cell and Chemical Biology, Leiden University, Medical Centre, Leiden, 2333, ZC, The Netherlands.

Published: January 2025

Daylength (i.e., photoperiod) provides essential information for seasonal adaptations of organisms. Earlier studies have demonstrated that photoperiod influences sleep in several species. Notably, photoperiod can change the excitatory/inhibitory balance in the brain, with long photoperiod exhibiting increased γ-aminobutyric-acid (GABA)-mediated excitation. In this study, we first investigated whether different photoperiods influence sleep and the sleep electroencephalogram (EEG) in mice, and, subsequently, whether these photoperiods alter GABAergic functioning by treating mice with diazepam (3 mg/kg, i.p.). EEG and electromyogram (EMG) recordings were conducted in mice well-adapted to long or short photoperiod (16:8 vs. 8:16 light-dark cycle) in baseline conditions, after 4-h sleep deprivation, and following diazepam administration. Different photoperiods led to a redistribution of sleep and wakefulness in 24-h albeit without altering the overall amount of vigilance states; during darkness, mice exposed to the long photoperiod were more awake and showed very little rapid-eye-movement (REM) sleep compared to the short photoperiod. Furthermore, an overall lower EEG power density, across all vigilance states, was found in the long compared to short photoperiod. After diazepam treatment, slow-wave-activity (SWA) in NREM sleep was suppressed independent of the photoperiod. However, following diazepam administration, mice showed more REM sleep in the short photoperiod, and increased EEG power density in the slower frequencies (2.5-7 Hz), during wakefulness in the long photoperiod. These results demonstrate that photoperiod can affect the diazepam-induced changes on sleep architecture and EEG, suggesting that treatments with GABA agonists exert dissimilar effects depending on the photoperiod. Future studies are warranted to explore potential photoperiod effects in humans which could have consequences for the treatment of anxiety and sleep disturbances.

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http://dx.doi.org/10.1038/s41401-024-01440-3DOI Listing

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