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地西泮对睡眠的影响取决于光照周期。

The effects of diazepam on sleep depend on the photoperiod.

作者信息

Panagiotou Maria, Meijer Johanna H, Deboer Tom

机构信息

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

Erasmus University College, Erasmus School of Social and Behavioural Sciences, Life Sciences Department, Erasmus University Rotterdam, Rotterdam, 3011, HP, the Netherlands.

出版信息

Acta Pharmacol Sin. 2025 Apr;46(4):892-903. doi: 10.1038/s41401-024-01440-3. Epub 2025 Jan 3.

DOI:10.1038/s41401-024-01440-3
PMID:39753982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11950407/
Abstract

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.

摘要

日照长度(即光周期)为生物体的季节性适应提供了重要信息。早期研究表明,光周期会影响多个物种的睡眠。值得注意的是,光周期可改变大脑中的兴奋/抑制平衡,长光周期表现出γ-氨基丁酸(GABA)介导的兴奋性增加。在本研究中,我们首先研究了不同光周期是否会影响小鼠的睡眠和睡眠脑电图(EEG),随后研究了这些光周期是否通过给小鼠注射地西泮(3 mg/kg,腹腔注射)来改变GABA能功能。在基线条件下、4小时睡眠剥夺后以及地西泮给药后,对适应长或短光周期(16:8与8:16明暗循环)的小鼠进行EEG和肌电图(EMG)记录。不同的光周期导致24小时内睡眠和觉醒的重新分布,尽管没有改变警觉状态的总量;在黑暗期间,与短光周期相比,暴露于长光周期的小鼠更清醒,快速眼动(REM)睡眠很少。此外,与短光周期相比,长光周期在所有警觉状态下的EEG功率密度总体较低。地西泮治疗后,非快速眼动睡眠中的慢波活动(SWA)受到抑制,与光周期无关。然而,地西泮给药后,短光周期的小鼠表现出更多的REM睡眠,长光周期清醒期间较慢频率(2.5-7 Hz)的EEG功率密度增加。这些结果表明,光周期可影响地西泮诱导的睡眠结构和EEG变化,提示GABA激动剂治疗根据光周期产生不同的效果。未来有必要开展研究,探索光周期对人类的潜在影响,这可能会对焦虑和睡眠障碍的治疗产生影响。

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