Department of Neurosciences, The Scripps Research Institute, La Jolla, CA.
Sleep. 2019 Apr 1;42(4). doi: 10.1093/sleep/zsz020.
Insomnia is a prominent complaint in patients with alcohol use disorders (AUD). However, despite the importance of sleep in the maintenance of sobriety, treatment options for sleep disturbance associated with a history of AUD are currently limited. Recent clinical trials have demonstrated that suvorexant, a dual Hct/OX receptor antagonist, normalizes sleep in patients with primary insomnia; yet, its potential for the treatment of sleep pathology associated with AUD has not been investigated in either preclinical or clinical studies.
This study employed a model whereby ethanol vapor exposure or control conditions were administered for 8 weeks to adult rats. Waking event-related oscillations (EROs) and EEG sleep were evaluated at baseline before exposure and again following 24 hr of withdrawal from the exposure. Subsequently, the ability of vehicle (VEH) and two doses (10, 30 mg/kg IP) of suvorexant to modify EROs, sleep, and the sleep EEG was investigated.
After 24 hr following EtOH withdrawal, the ethanol-treated group had increases in waking ERO θ and β activity, more fragmented sleep (shorter duration and increased frequency of slow wave (SW) and rapid eye movement [REM] sleep episodes), and increased θ and β power in REM and SW sleep. Suvorexant induced a dose-dependent decrease in the latency to REM and SW sleep onsets but also produced REM and SW sleep fragmentation and increased β energy in waking EROs when compared with VEH.
Taken together, these studies suggest that suvorexant has overall sleep-promoting effects, but it may exacerbate some aspects of sleep and EEG pathology.
失眠是酒精使用障碍（AUD）患者的突出主诉。然而，尽管睡眠对于保持清醒状态非常重要，但目前针对与 AUD 相关的睡眠障碍的治疗选择非常有限。最近的临床试验表明，双重 Hct/OX 受体拮抗剂苏沃雷生可使原发性失眠患者的睡眠正常化；然而，它在临床前或临床研究中尚未被用于治疗与 AUD 相关的睡眠病理学。
本研究采用了一种模型， whereby 8 周内对成年大鼠进行乙醇蒸气暴露或对照条件处理。在暴露前的基线评估清醒时事件相关振荡（EROs）和 EEG 睡眠，然后在暴露后 24 小时戒断后再次评估。随后，研究了载体（VEH）和两种剂量（10、30 mg/kg IP）的苏沃雷生对 EROs、睡眠和睡眠 EEG 的影响。
在乙醇戒断后 24 小时，乙醇处理组的清醒 ERO θ 和 β 活动增加，睡眠碎片化（持续时间缩短，慢波（SW）和快速眼动（REM）睡眠发作的频率增加），以及 REM 和 SW 睡眠中的 θ 和 β 功率增加。与 VEH 相比，苏沃雷生诱导 REM 和 SW 睡眠潜伏期的剂量依赖性降低，但也导致 REM 和 SW 睡眠碎片化，并增加清醒 ERO 中的 β 能量。
综上所述，这些研究表明，苏沃雷生具有整体的促眠作用，但可能会加重某些方面的睡眠和 EEG 病理学。
