Endogenous Melatonin is Not Obligatory for the Regulation of the Rat Sleep-Wake Cycle
Endogenous Melatonin is Not Obligatory for the Regulation of the Rat Sleep-Wake Cycle
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DOI：
10.1093/sleep/33.6.833
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发表时间：
2010-06-01
期刊：
影响因子：
5.6
通讯作者：
Sugden, David
中科院分区：
文献类型：
--
作者：
Fisher, Simon P.;Sugden, David
研究目的：尽管褪黑素和褪黑素受体激动剂已在临床上用于治疗失眠，但内源性褪黑素在调节睡眠-觉醒周期中的作用仍不确定。一些临床病例报告表明，夜间褪黑激素分泌减少与睡眠中断有关，但摘除松果体对实验动物的结果各不相同。设计：本研究考察了松果体摘除对植入放射性发射器的大鼠白天睡眠-觉醒周期的影响，以便在家中不受限制地连续测量皮质脑电、肌电和核心温度(TC)。测量和结果：松果体摘除后TC略有下降(0.2摄氏度)，但显著降低。与假手术对照组相比，松果体摘除大鼠的运动活动、觉醒、非快速眼动(NREM)睡眠和快速眼动(REM)睡眠的总量和日分布没有改变。通过确定觉醒、非快速眼动睡眠和快速眼动睡眠的持续时间和频率来衡量睡眠巩固程度也没有变化。NREM睡眠期间的脑电功率谱没有变化，但REM睡眠期间的theta功率(5-8赫兹)显著下降。结论：我们的数据没有提供证据表明内源性循环褪黑素在调节大鼠睡眠-觉醒周期中起作用。然而，由于皮质theta振荡是在海马区的CA1-3层产生的，已知的神经元表达褪黑素受体，这表明松果体切除后褪黑素的缺乏影响了这些神经元的功能，并与先前的工作一致，表明内源性褪黑素是海马生理的重要调节因子。
Study Objectives: Though melatonin and melatonin receptor agonists are in clinical use and under development for treating insomnia, the role of endogenous melatonin in the regulation of the sleep-wake cycle remains uncertain. Some clinical case reports suggest that reduced nocturnal melatonin secretion is linked to sleep disruption, but pineal-gland removal in experimental animals has given variable results.Design: The present study examined the effects of pinealectomy on the diurnal sleep-wake cycle of rats implanted with a radiotransmitter to allow continuous measurement of cortical electroencephalogram, electromyogram, and core temperature (Tc) without restraint in their home cages.Measurements and Results: Tc was slightly (0.2 degrees C) but significantly lower after pineal removal. The total amount and diurnal distribution of locomotor activity, wake, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were unaltered in pinealectomized rats compared to sham-operated controls. Sleep consolidation measured by determining wake, NREM sleep, and REM sleep bout length and frequency was also unchanged. The EEG power spectrum during NREM sleep was unchanged, but a significant decrease in theta power (5-8 Hz) during REM sleep episodes was found.Conclusions: Our data provide no evidence that endogenous circulating melatonin plays a role in regulating the sleep-wake cycle in rats. However, because cortical theta oscillations are generated in the CA1-3 layer of the hippocampus, neurons known to express melatonin receptors, this suggests that a lack of melatonin following pineal removal influences the function of these neurons and is consistent with previous work suggesting that endogenous melatonin is an important regulator of hippocampal physiology.