Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Neuropharmacology. 2020 Mar 1;164:107913. doi: 10.1016/j.neuropharm.2019.107913. Epub 2019 Dec 14.
Alcohol is commonly used as a sleep inducer/aid by humans. However, individuals diagnosed with alcohol use disorders have sleep problems. Few studies have examined the effect of ethanol on physiological features of sedation and anesthesia, particularly at high doses. This study used polysomnography and a rapid, unbiased scoring of vigilance states with an automated algorithm to provide a thorough characterization of dose-dependent acute ethanol effects on sleep and electroencephalogram (EEG) power spectra in C57BL/6J male mice. Ethanol had a narrow dose-response effect on sleep. Only a high dose (4.0 g/kg) produced a unique, transient state that could not be characterized in terms of canonical sleep-wake states, so we dubbed this novel state Drug-Induced State with a Characteristic Oscillation in the Theta Band (DISCO-T). After this anesthetic effect, the high dose of alcohol promoted NREM sleep by increasing the duration of NREM bouts while reducing wake. REM sleep was differentially responsive to the circadian timing of ethanol administration. EEG power spectra proved more sensitive to ethanol than sleep measures as there were clear effects of ethanol at 2.0 and 4.0 g/kg doses. Ethanol promoted delta oscillations and suppressed faster frequencies, but there were clear, differential effects on wake and REM EEG power based on the timing of the ethanol injection. Understanding the neural basis of the extreme soporific effects of high dose ethanol may aid in treating acute toxicity brought about by patterns of excessive binge consumption commonly observed in young people.
酒精是人类常用的诱导/辅助睡眠的物质。然而,被诊断患有酒精使用障碍的个体存在睡眠问题。很少有研究研究乙醇对镇静和麻醉的生理特征的影响,尤其是在高剂量下。本研究使用多导睡眠图和快速、无偏的警觉状态评分以及自动化算法,全面描述了 C57BL/6J 雄性小鼠中,急性乙醇剂量依赖性对睡眠和脑电图(EEG)频谱的影响。
乙醇对睡眠的剂量反应狭窄。只有高剂量(4.0 g/kg)产生一种独特的、短暂的状态,不能根据经典的睡眠-觉醒状态来描述,因此我们将这种新状态命名为具有特征性θ波段振荡的药物诱导状态(DISCO-T)。在这种麻醉作用之后,高剂量的酒精通过增加 NREM 发作的持续时间,同时减少觉醒,促进 NREM 睡眠。REM 睡眠对乙醇给药的昼夜节律时间有不同的反应。
脑电图功率谱比睡眠测量对乙醇更敏感,因为在 2.0 和 4.0 g/kg 剂量下,乙醇有明显的影响。乙醇促进了 delta 振荡,并抑制了更快的频率,但根据乙醇注射的时间,对觉醒和 REM 脑电图功率有明显的、不同的影响。
了解高剂量乙醇极度催眠作用的神经基础,可能有助于治疗年轻人中常见的过度狂欢式饮酒模式引起的急性毒性。