Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo, Uruguay.
Sleep Med Rev. 2010 Oct;14(5):319-27. doi: 10.1016/j.smrv.2009.10.003. Epub 2010 Feb 12.
Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches it is currently accepted that serotonin (5-HT) functions to promote waking (W) and to inhibit rapid-eye movement sleep (REMS). The serotonin-containing neurons of the dorsal raphe nucleus (DRN) provide part of the serotonergic innervation of the telencephalon, diencephalon, mesencephalon and rhombencephalon of laboratory animals and man. The DRN has been subdivided into several clusters on the basis of differences in cellular morphology, expression of other neurotransmitters and afferent and efferent connections. These differences among subpopulations of 5-HT neurons may have important implications for neural mechanisms underlying 5-HT modulation of sleep and waking. The DRN contains 5-HT and non-5-HT neurons. The latter express a variety of substances including dopamine, γ-aminobutyric acid (GABA) and glutamate. In addition, nitric oxide and a number of neuropeptides have been characterized in the DRN. Available evidence tends to indicate that non-5-HT cells contribute to the regulation of the activity of 5-HT neurons during the sleep-wake cycle through local circuits and/or their mediation of the effects of afferent inputs. Mutant mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of REMS than their wild-type couterparts. 5-HT(2A) and 5-HT(2C) receptor knockout mice show a significant increase of W and a reduction of slow wave sleep that is related, at least in part, to the increased release of norepinephrine and dopamine. A normal circadian sleep pattern is observed in 5-HT(7) receptor knockout mice; however, the mutants spend less time in REMS. Local microinjection of 5-HT(1B), 5-HT(2A/2C), 5-HT(3) and 5-HT(7) receptor agonists into the DRN selectively suppresses REMS in the rat. In contrast, microinjection of 5-HT(1A) receptor agonists promotes REMS. Similarly, local administration of the melanin-concentrating hormone or the GABA(A) receptor agonist muscimol produces an increase of REMS in the rat. Presently, there are no data on the effect of local infusion into the DRN of noradrenergic, dopaminergic, histaminergic, orexinergic and cholinergic agonists on sleep variables in laboratory animals.
基于电生理学、神经化学、遗传学和神经药理学的方法，目前人们普遍认为 5-羟色胺（5-HT）的功能是促进觉醒（W）并抑制快速眼动睡眠（REMS）。背侧中缝核（DRN）中的 5-HT 能神经元为实验室动物和人类的端脑、间脑、中脑和后脑提供部分 5-HT 能神经支配。DRN 已根据细胞形态、其他神经递质的表达以及传入和传出连接的差异，分为几个簇。这些 5-HT 神经元亚群之间的差异可能对 5-HT 调节睡眠和觉醒的神经机制具有重要意义。DRN 包含 5-HT 和非 5-HT 神经元。后者表达多种物质，包括多巴胺、γ-氨基丁酸（GABA）和谷氨酸。此外，DRN 中还描述了一氧化氮和许多神经肽。现有证据表明，非 5-HT 细胞通过局部回路和/或其对传入输入效应的介导，有助于调节睡眠-觉醒周期中 5-HT 神经元的活动。不表达 5-HT(1A)或 5-HT(1B)受体的突变小鼠比它们的野生型对照表现出更多的 REMS。5-HT(2A)和 5-HT(2C)受体敲除小鼠表现出 W 的显著增加和慢波睡眠的减少，这至少部分与去甲肾上腺素和多巴胺的释放增加有关。5-HT(7)受体敲除小鼠观察到正常的昼夜睡眠模式；然而，突变体在 REMS 中花费的时间更少。5-HT(1B)、5-HT(2A/2C)、5-HT(3)和 5-HT(7)受体激动剂在 DRN 中的局部微注射选择性抑制大鼠的 REMS。相比之下，5-HT(1A)受体激动剂的微注射促进 REMS。同样，黑皮质素或 GABA(A)受体激动剂 muscimol 的局部给药会增加大鼠的 REMS。目前，尚无关于 DRN 内局部输注去甲肾上腺素能、多巴胺能、组胺能、食欲素能和胆碱能激动剂对实验室动物睡眠变量影响的数据。
