Wake-promoting and sleep-suppressing actions of hypocretin (orexin):: Basal forebrain sites of action
Wake-promoting and sleep-suppressing actions of hypocretin (orexin):: Basal forebrain sites of action
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DOI：
10.1016/s0306-4522(01)00319-0
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Berridge, CW
中科院分区：
文献类型：
--
作者：
España, RA;Baldo, BA;Berridge, CW
下丘脑泌素（食欲素）是新近鉴定的由下丘脑泌素- I和下丘脑泌素-2两种肽组成的肽家族。最近的观察表明，这些肽参与行为状态的调节。例如，这些肽存在于与前脑神经元和行为活动状态的调节相关的多种脑区域中。此外，当输注到清醒动物的侧脑室时，下丘脑泌素-1增加了清醒的持续时间，超过了在溶剂处理的动物中观察到的持续时间。以前的研究仅限于检查下丘脑泌素-1在清醒动物中的睡眠-觉醒效应。目前，下丘脑泌素-2的睡眠-觉醒效应以及下丘脑泌素在睡眠动物中启动觉醒的程度尚不清楚。为了更好地描述hypocretins的促醒作用，目前的研究检查了不同剂量的睡眠-觉醒效应（0.007、0.07和0.7 nmol）下丘脑泌素-1和下丘脑泌素-2给药至睡眠大鼠时下丘脑泌素-1和下丘脑泌素-2注入侧脑室引起短的潜伏期，（0.7 nmol下丘脑泌素-1;从120-s输注开始93 +/- 30 s）脑电图、肌电图和清醒行为指数增加。这些输注也使慢波和快眼动睡眠显著减少。Hypocretin-1在这些作用中比hypocretin-2更有效。有趣的是，下丘脑泌素-1输注到第四脑室引起不太强烈的觉醒，其发生的潜伏期比输注到侧脑室更长。这些后者的观察表明前脑的行动网站参与下丘脑泌素-1-诱导waking.Within前脑，各种基底前脑结构，包括内侧视前区，内侧隔区和无名质，接受中度下丘脑泌素神经支配。因此，额外的研究检查了双侧下丘脑泌素-1输注到这些基底前脑结构中的睡眠-觉醒效应。稳健的增加清醒后，观察到的输液，但不是外面，内侧隔区，内侧视前区，区和substantia innominata.These结果表明一个潜在的突出作用hypocretins在睡眠-觉醒调节通过某些基底前脑结构内的行动，并与研究表明hypocretins在睡眠/觉醒障碍的突出作用是一致的。(C)2001年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
he hypocretins (orexins) are a newly identified peptide family comprised of two peptides, hypocretin- I and hypocretin-2. Recent observations suggest an involvement of these peptides in the regulation of behavioral state. For example, these peptides are found in a variety of brain regions associated with the regulation of forebrain neuronal and behavioral activity states. Furthermore, when infused into the lateral ventricles in awake animals, hypocretin-1 elicits increased duration of waking beyond that observed in vehicle-treated animals. Previous studies have been limited to an examination of the sleep-wake effects of hypocretin-1 in awake animals. Currently, the sleep-wake effects of hypocretin-2 and the extent to which hypocretins can initiate waking in the sleeping animal remain unclear. To better characterize the wake-promoting actions of the hypocretins, the current studies examined the sleep-wake effects of varying doses (0.007, 0.07 and 0.7 nmol) of hypocretin-1 and hypocretin-2 when administered into sleeping rats (e.g. remote-controlled infusions).Infusions of hypocretin-1 and hypocretin-2 into the lateral ventricles elicited a short latency (0.7 nmol hypocretin-1; 93 +/- 30 s from the start of the 120-s infusion) increase in electroencephalographic, electromyographic, and behavioral indices of waking. These infusions also produced substantial decreases in slow-wave and rapid-eye movement sleep. Hypocretin-1 was more potent than hypocretin-2 in these actions. Interestingly, hypocretin-1 infused into the fourth ventricle elicited less robust waking which occurred with a longer latency than infusions into the lateral ventricles. These latter observations suggest a forebrain site of action participates in hypocretin-1-induced waking.Within the forebrain, a variety of basal forebrain structures, including the medial preoptic area, the medial septal area and the substantia innominata, receive a moderate hypocretin innervation. Therefore, additional studies examined the sleep-wake effects of bilateral hypocretin-1 infusions into these basal forebrain structures. Robust increases in waking were observed following infusions into, but not outside, the medial septal area, the medial preoptic, area and the substantia innominata.These results indicate a potentially prominent role of hypocretins in sleep-wake regulation via actions within certain basal forebrain structures and are consistent with studies indicating a prominent role of hypocretins in sleep/arousal disorders. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.