Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans
Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans
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DOI：
10.1113/jphysiol.2004.073742
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发表时间：
2004-11-15
影响因子：
5.5
通讯作者：
Dijk, DJ
中科院分区：
文献类型：
--
作者：
Rajaratnam, SMW;Middleton, B;Dijk, DJ
源自松果体并由位于视交叉上核的昼夜节律起搏器驱动的血浆褪黑激素的节律与人类睡眠倾向和睡眠纺锤体活动的昼夜节律（约24小时）变化密切相关。我们研究了褪黑激素对睡眠倾向、结构、持续时间和脑电图活动变化的影响，其中睡眠被安排在生物日期间开始，即内源性褪黑激素浓度较低时。两次为期 14 天的试验是在环境调度设施中进行的。每项试验均包括两次昼夜节律阶段评估、基线睡眠和九次接近黑暗的 16 小时睡眠机会（16:00-08:00）。招募了 8 名没有睡眠问题的健康男性志愿者（24.4 +/- 4.4 岁），并在前 8 个 16 小时睡眠机会开始时服用褪黑激素（1.5 毫克）或安慰剂。在褪黑激素治疗期间，16小时睡眠机会中前8小时的睡眠时间增加了2小时。在两种情况下，每 16 小时的睡眠时间没有显着差异，均接近 8.7 小时的渐近值。快速眼动（REM）睡眠的百分比不受褪黑激素的影响，但第2阶段睡眠和睡眠纺锤波活动的百分比增加，第3阶段睡眠的百分比减少。在清洗晚上，褪黑激素引起的睡眠时间提前持续存在，但比前一个治疗晚上要小，并且与内源性褪黑激素节律的提前一致。这些数据证明了褪黑激素具有强大、直接的促进睡眠和昼夜节律作用，且不伴随睡眠持续时间的变化，并支持使用褪黑激素治疗睡眠障碍，其中褪黑激素的昼夜节律相对于所需的睡眠时间延迟。
The rhythm of plasma melatonin originating from the pineal gland and driven by the circadian pacemaker located in the suprachiasmatic nucleus is closely associated with the circadian (approximately 24 h) variation in sleep propensity and sleep spindle activity in humans. We investigated the contribution of melatonin to variation in sleep propensity, structure, duration and EEG activity in a protocol in which sleep was scheduled to begin during the biological day, i.e. when endogenous melatonin concentrations are low. The two 14 day trials were conducted in an environmental scheduling facility. Each trial included two circadian phase assessments, baseline sleep and nine 16 h sleep opportunities (16.00-08.00 h) in near darkness. Eight healthy male volunteers (24.4 +/- 4.4 years) without sleep complaints were recruited, and melatonin (1.5 mg) or placebo was administered at the start of the first eight 16 h sleep opportunities. During melatonin treatment, sleep in the first 8 h of the 16 h sleep opportunities was increased by 2 h. Sleep per 16 h was not significantly different and approached asymptotic values of 8.7 h in both conditions. The percentage of rapid eye movement (REM) sleep was not affected by melatonin, but the percentage of stage 2 sleep and sleep spindle activity increased, and the percentage of stage 3 sleep decreased. During the washout night, the melatonin-induced advance in sleep timing persisted, but was smaller than on the preceding treatment night and was consistent with the advance in the endogenous melatonin rhythm. These data demonstrate robust, direct sleep-facilitating and circadian effects of melatonin without concomitant changes in sleep duration, and support the use of melatonin in the treatment of sleep disorders in which the circadian melatonin rhythm is delayed relative to desired sleep time.