Akanmu Moses A, Honda Kazuki
Department of Biosystem Regulation, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Brain Res. 2005 Jun 28;1048(1-2):138-45. doi: 10.1016/j.brainres.2005.04.064.
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, [Ala11]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, [Ala11]orexin-B, on the sleep-wake cycle were investigated. ICV infusion of [Ala11]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 1 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.
食欲素A和B是一对神经肽，通过两种1型和2型食欲素受体参与介导进食和觉醒行为的调节。我们已经确定了新开发的选择性2型食欲素受体激动剂[Ala11]食欲素-B对大鼠睡眠-觉醒周期的觉醒作用。研究了向第三脑室脑室内（ICV）注入新型2型食欲素受体选择性激动剂[Ala11]食欲素-B对睡眠-觉醒周期的影响。在光照期（11:00-16:00）向ICV注入[Ala11]食欲素-B（1、10和40纳摩尔），剂量依赖性地导致清醒时长分别显著增加46.9%（n = 5，P < 0.05）、159.2%（n = 4，P < 0.01）和163.6%（n = 7，P < 0.01），并且所有剂量下快速眼动（REM）睡眠（P < 0.01）和非快速眼动睡眠（P < 0.01）均显著减少。相比之下，以相同剂量（1、10和40纳摩尔）向ICV注入食欲素B分别使清醒时长增加了16.6%（n = 6，无显著性差异）、99.8%（n = 6，P < 0.05）和72.0%（n = 4，P < 0.05）。此外，通过1型和2型食欲素受体发挥相似效力作用的食欲素-A，在剂量分别为0.1、1和10纳摩尔时，使清醒时长分别显著增加17.1%（n = 6，P < 0.05）、184.0%（n = 6，P < 0.01）和228.6%（n = 6，P < 0.01）。此外，清醒的增强伴随着REM睡眠和非REM睡眠的显著减少。这些发现表明2型食欲素受体在睡眠-觉醒状态和行为反应的调节中起重要作用。
