Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats
Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats
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DOI：
10.1016/j.brainres.2005.04.064
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发表时间：
2005-06-28
期刊：
影响因子：
2.9
通讯作者：
Honda, K
中科院分区：
文献类型：
--
作者：
Akanmu, MA;Honda, K
食欲素A和B是一对神经肽，涉及通过两种食欲素受体1型和2型介导的进食和唤醒行为的调节。我们测定了新开发的选择性食欲素受体2型激动剂[Ala（11）]orexin-B对大鼠睡眠-觉醒周期的唤醒作用。研究了新型食欲素受体2型选择性激动剂[Ala（11）]orexin-B在第三脑室侧脑室（ICV）内输注对睡眠-觉醒周期的影响。在光照期间（11：00-16：00）ICV输注[Ala（11）]orexin-B（1、10和40 nmol）剂量依赖性地导致觉醒时间分别显著增加46.9%（n = 5，P < 0.05）、159.2%（n = 4，P < 0.01）和163.6%（n = 7，P < 0.01），并且所有剂量均显著减少快速眼动（REM）（P < 0.01）和非REM睡眠（P < 0.01）。相反，ICV输注相同剂量（1、10和40 nmol）的食欲素B分别导致觉醒增加16.6%（n = 6，无显著性）、99.8%（n = 6，P < 0.05）和72.0%（n = 4，P < 0.05）。此外，食欲素-A通过具有类似效力的食欲素受体I型和食欲素受体2型发挥其作用，导致觉醒持续时间显著增加17.1%。0.1、1和10 nmol组的细胞增殖率分别为184.0%（n = 6，P < 0.01）和228.6%（n = 6，P < 0.01）。此外，觉醒的增强伴随着REM和非REM睡眠的显着减少。这些结果表明，食欲素受体2型在调节睡眠-觉醒状态和行为反应中起着重要作用。(c)2005 Elsevier B. V.保留所有权利。
Orexins A and B are a pair of neuropeptides implicated in the regulation of feeding and arousal behavior mediated through two orexin receptors type 1 and type 2. We have determined the arousal effects of newly developed selective orexin receptor type 2 agonist, [Ala(11)]orexin-B, on the sleep-wake cycle in rats. The effects of third ventricle intracerebroventricular (ICV) infusion of the novel orexin receptor type 2 selective agonist, [Ala(11)]orexin-B, on the sleep-wake cycle were investigated. ICV infusion of [Ala(11)]orexin-B (1, 10 and 40 nmol) during the light period (11:00-16:00) dose-dependently resulted in a significant increase in wake duration by 46.9% (n = 5, P < 0.05), 159.2% (n = 4, P < 0.01) and 163.6% (n = 7, P < 0.01)), respectively, and a significant decrease in rapid eye movement (REM) (P < 0.01) and non-REM sleep (P < 0.01) for all doses. In contrast, ICV infusion of orexin B at the same doses (1, 10 and 40 nmol) caused a 16.6% (n = 6, non-significant), 99.8% (n = 6, P < 0.05) and 72.0% (n = 4, P < 0.05) increase in wakefulness, respectively. Moreover, orexin-A, which exerts its effects through orexin receptor type I and orexin receptor type 2 with similar potency, resulted in a significant increase in wakefulness duration by 17.1% (n = 6, P < 0.05), 184.0% (n = 6, P < 0.01) and 228.6% (n = 6, P < 0.01) at doses of 0.1, 1 and 10 nmol, respectively. Further, the enhancement of wakefulness was accompanied by a marked reduction in REM and non-REM sleep. These findings suggest that orexin receptor type 2 plays an important role in the modulation of sleep-wake state and behavioral responses. (c) 2005 Elsevier B.V. All rights reserved.