New aspects of the mechanism of emergence from anesthesia -A research for the antagonistic action of orexin, a cerebral excitatory neurotransmitter, against anesthesia-

据报道，食欲素具有增加摄食、保持清醒、缓解疼痛以及激活交感神经系统等多种作用。在食欲素的这些作用中，食欲素诱导的清醒维持可能有助于麻醉苏醒。在大脑中，有各种各样的唤醒系统，如去甲肾上腺素能、胆碱能、组胺能、血清素能和多巴胺能系统。据报道，胆碱能唤醒系统可能有助于异氟醚、七氟醚、异丙酚和神经轻素麻醉的出现。因此，我们将重点放在胆碱能系统与食欲能系统在麻醉出现中的作用上。从我们的研究中，我们得到了以下结果。1)异氟醚深度麻醉大鼠脑室内注射食欲素激活脑电图。2)下丘脑后部微量注射谷氨酸可通过作用于食欲素引起脑电图觉醒。3) orexin皂苷选择性破坏下丘脑外侧，降低了异氟烷的最低肺泡浓度。4)异氟醚剂量依赖性地增加了基底前脑的谷氨酸外排，而不是下丘脑后部和皮层。此外，在异氟醚麻醉下，微量注射谷氨酸受体激动剂AMPA，剂量依赖性地增加了乙酰胆碱（Ach）从皮质流出，这表明异氟醚的麻醉水平可能在异氟醚的抑制作用和该药物诱导的谷氨酸兴奋作用之间取得平衡。5)异氟醚麻醉下，基底前脑微量注射促食欲素可引起乙酰胆碱外排增加，激活脑电图。此外，在异氟醚麻醉下，电刺激胆碱能上升通路的起点——桥脑蒂被盖增加了脑皮质乙酰胆碱外排和脑电图觉醒。这些作用可被选择性食欲素-1受体拮抗剂SB334867拮抗。综上所述，我们认为食欲能系统可能通过胆碱能唤醒系统参与麻醉苏醒。少

Orexin has been reported to have the various actions of increases in feeding, maintenance of wakefulness, pain relief as well as activation of sympathetic nervous system. Among these actions of orexin, the maintenance of wakefulness induced by orexins might contribute to the emergence from anesthesia. In the brain, there are various arousal systems such as noradrenergic, cholinergic, histaminergic, serotonergic and dopaminergic systems. It has been reported that the cholinergic arousal system may contribute to the emergence from isoflurane, sevoflurane, propofol and neuroleptanestesia. Thus, we focused on the role of cholinergic system on the emergence from anesthesia in relation to orexinergic system. From our studies, we got the following results. 1) Intraventricular injection of orexin activated the electroencephalogram (EEG) under deep isoflurane anesthesia in the rat. 2) Microinjection of glutamate into the posterior hypothalamus induced EEG arousal through acting on the orexin ne … More urons. 3) The selective destruction of lateral hypothalamus with orexin-saporin decreased the minimum alveolar concentration of isoflurane. 4) Isoflurane dose-dependently increased the efflux of glutamate in the basal forebrain, not in the posterior hypothalamus and the cortex. Further, under isoflurane anesthesia, microinjection of AMPA, a glutamate receptor agonist, dose-dependently increased the efflux of acetylcholine (Ach) from the cortex, suggesting that the anesthetic level of isoflurane may be balanced between the inhibitory action of isoflurane and the excitatory action of glutamate induced by this agent. 5) Under isoflurane anesthesia, microinjection of orexins into the basal forebrain induced the increases in Ach efflux and activated EEG. In addition, the electrical stimulation of the pedunculopontine tegmentum, the origin of cholinergic ascending pathways, increased the cortical Ach efflux and the EEG arousal under isoflurane anesthesia. These actions were antagonized by SB334867, a selective orexin-1 receptor antagonist. From all the findings, we concluded that orexinergic system may contribute to the emergence from anesthesia through cholinergic arousal system. Less