最新一期美国《神经科学杂志》发表复旦大学医学神经生物学国家重点实验室黄志力课题组一项研究成果，这一成果有望有效治疗因换床导致无法入睡的失眠症。

医学上把这种失眠现象称为“第一晚效应”。资料显示，随着工业化进程的加快，社会竞争、工作压力，不良夜生活习惯及人口老龄化等原因，全球三分之一的人存在睡眠问题，其中不少人因经常出差不能在习惯的床上睡眠或入睡前情绪改变，精神亢奋或紧张，难以入眠，深陷“第一晚效应”痛苦之中，不能自拔，严重影响次日工作效率和身体健康。

研究表明，多巴胺系统调控运动、情感、奖赏、认知等生理过程与药物成瘾关系密切。但人们对”多巴胺“在睡眠觉醒中的作用及机制认识非常有限。复旦大学医学神经生物学国家重点实验室黄志力课题组研究人员曲卫敏、徐昕红等，运用高度自动化睡眠觉醒解析系统，记录一种已经基因剔除了“多巴胺D2受体”小鼠的睡眠过程，并结合药理学等手段，从基因到行为解析了多巴胺D2受体在睡眠觉醒调控中的作用。

结果发现：与正常小鼠（野生型小鼠）相比，剔除了“多巴胺D2受体”的小鼠，活动期维持觉醒困难，睡眠量增加。为模拟人在新环境下（如出差住宿等）出现“换床后”失眠现象，即“第一晚效应”，研究人员更换动物居住环境，考察小鼠在新环境中的睡眠行为。结果显示：多巴胺D2受体正常的小鼠面对新环境刺激，极为不习惯，入睡困难，而剔除了“多巴胺D2受体”的小鼠，则“高枕无忧”，迅速入睡。

该研究成果揭示大脑内蛋白质多巴胺D2受体是调控觉醒行为的重要受体，丰富和发展了医学界有关睡眠、觉醒调节理论系统，为临床治疗人群中普遍存在的“换床入睡难”的“第一晚效应”顽症，提供了新思路和新方法。

原文出处：

The Journal of Neuroscience doi:10.1523/JNEUROSCI.4936-09.2010

Essential Role of Dopamine D2 Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice
Wei-Min Qu,1 Xin-Hong Xu,1 Ming-Ming Yan,1 Yi-Qun Wang,1 Yoshihiro Urade,2 and Zhi-Li Huang1

1Department of Pharmacology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai 200032, China, and 2Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan

Dopamine (DA) and its D2 receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep–wake regulation remain unclear. Herein we investigated the role of D2R in sleep–wake regulation by using D2R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D2R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75–2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D2R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D2R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D2R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D2R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.