Studies on the role of orexin in the brain vigilance levels.

食欲素A和食欲素B是调节食欲系统的新型神经肽。最近的研究表明，犬嗜睡症是由食欲素-2受体基因缺陷引起的，并且食欲素前基因敲除小鼠表现出与人类和犬嗜睡症相似的行为。含有食欲素的神经元位于下丘脑外侧区，密集地投射到去肾上腺素能蓝斑、多巴胺能腹侧被盖区、血清素能背中叶核和组胺能结节乳头核。脑室内注射促食欲素A和促食欲素B对正常雄性大鼠有明显的唤醒作用。连续3天，以10 μl/h的速度静脉滴注生理盐水，监测皮质脑电图和颈部肌电图。在5 h的昼夜周期内，分别更换促食素A （0.1 ~ 10 nmol）和促食素B （1 ~ 40 nmol）。静脉输注生理盐水。在10 nmol剂量下，食欲素A显著增加了228.6%的清醒量（p<0.01），而在相同剂量下，食欲素B比基线值增加了99.8% （p<0.01）。两种增食欲素都引起了清醒程度的剂量依赖性增加。觉醒的增强是由于睡眠的明显减少。数据表明，在相同剂量下，食欲素A比食欲素B更能引起兴奋状态。由于食欲素A对食欲素-1和食欲素-2受体具有相同的亲和力，而食欲素B只对食欲素-2受体具有亲和力，因此外源性给予食欲素A可能比食欲素B更有效地增强唤醒状态。综上所述，食欲素A和食欲素B可能通过食欲素-1和食欲素-2受体位点在调节睡眠-觉醒周期中发挥重要的生理作用。

Orexins A and B are novel neuropeptides which are known to regulate the appetite system. Recent studies showed that canine narcolepsy is caused by deficit in the orexin-2 receptor gene, and that prepro-orexin knock-out mice exhibited similar behavior to human and canine narcoleptics. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the noradrenergic locus coeruleus, dopaminergic ventral tegmental area, serotonergic dorsal raphe nuclei and histaminergic tuberomammillary nucleus. Intracerebroventricular (icv) infusion of orexins A and B induced significant arousal effect in the freely behaving normal-male Sprague-Dawley rats. Cortical EEG and neck EMG were monitored for three consecutive days , during continuous icv saline infusion at a rate of 10 μl/h. For 5-h diurnal period, either orexin A (0.1-10 nmol) or B ( 1-40 nmol) replaced. the icv infusion of saline. Orexin A at the dose of 10 nmol markedly increased the amount of wakefulness by 228.6% (p<0.01) whereas orexin B at the same dose caused an increase of 99.8% (p<0.01) over the baseline value. Both orexins caused dose-dependent increases in wakefulness. The enhancement of arousal was due to a marked reduction in sleep. The data indicate that orexin A is more effective in causing a state of arousal than orexin B at the same dose. Since orexin A has equal affinity for both the orexin-1 and orexin-2 receptors but orexin B only shows affinity for the orexin-2 receptor, thus exogenous administration of orexin A might be more effective in enhancing a state of arousal than orexin B.In conclusion, the results suggest that orexins A and B may play important physiological roles in the regulation of sleep-waking cycle through both the orexin-1 and orexin-2 receptor sites.