Arai Mayuko, Kent Brianne A
Department of Psychology, Simon Fraser University, Burnaby, Canada.
Institute for Neuroscience and Neurotechnology, Simon Fraser University, Burnaby, Canada.
Sleep Adv. 2025 May 28;6(2):zpaf031. doi: 10.1093/sleepadvances/zpaf031. eCollection 2025 Apr.
Trazodone is an antidepressant with robust hypnotic effects, frequently prescribed off-label to treat insomnia. Trazodone has gained recent attention in the context of neurodegenerative diseases because sleep has been proposed as a novel target for disease-modifying therapeutics. Preclinical research in rodents examining the effects of trazodone on sleep is limited, so here we aimed to develop a translationally focused protocol to study the sleep-promoting effects of trazodone in mice.
We investigated the effects of voluntary oral trazodone administration at doses of 10, 40, and 60 mg/kg on sleep in C57BL/6J mice ( = 15; females = 6; age 10-13 months). Mice were dosed with trazodone for 6 consecutive nights, while being recorded with intracranially implanted 2-channel electroencephalogram (EEG) and electromyography (EMG). EEG/EMG recordings were analyzed for time spent in each vigilance state and power spectra.
A single dose of trazodone, administered prior to the onset of the 12-h rest phase, dose-dependently increased non-rapid eye movement (NREM) sleep and delta power during NREM sleep, at the expense of rapid eye movement (REM) sleep. These effects on sleep persisted after six consecutive days of dosing, albeit to a lesser extent.
We have validated a novel voluntary oral administration protocol for trazodone use in mice and have shown that trazodone effectively promotes NREM in mice. Our novel protocol will be useful for future research investigating the effects of trazodone on sleep in mouse models of disease.
曲唑酮是一种具有强大催眠作用的抗抑郁药，常被超说明书用药用于治疗失眠。在神经退行性疾病的背景下，曲唑酮最近受到了关注，因为睡眠已被提议作为疾病修饰疗法的一个新靶点。在啮齿动物中研究曲唑酮对睡眠影响的临床前研究有限，因此我们旨在制定一个以转化为重点的方案，以研究曲唑酮在小鼠中的促睡眠作用。
我们研究了10、40和60mg/kg剂量的曲唑酮自愿口服给药对C57BL/6J小鼠（n = 15；雌性 = 6；年龄10 - 13个月）睡眠的影响。小鼠连续6晚服用曲唑酮，同时通过颅内植入的双通道脑电图（EEG）和肌电图（EMG）进行记录。对EEG/EMG记录进行分析，以确定每个警觉状态下的时间和功率谱。
在12小时休息期开始前给予单剂量曲唑酮，剂量依赖性地增加了非快速眼动（NREM）睡眠以及NREM睡眠期间的δ波功率，代价是快速眼动（REM）睡眠减少。连续给药6天后，这些对睡眠的影响仍然存在，尽管程度较小。
我们验证了一种用于小鼠的曲唑酮新型自愿口服给药方案，并表明曲唑酮能有效促进小鼠的NREM睡眠。我们的新方案将有助于未来研究曲唑酮在疾病小鼠模型中对睡眠的影响。
