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，食欲素具有增加进食、维持清醒、缓解疼痛以及激活交感神经系统的各种作用。在食欲素的这些作用中，食欲素诱导的觉醒的维持可能有助于从麻醉中苏醒。在大脑中，存在各种唤醒系统，例如去甲肾上腺素能、胆碱能、组胺能、多巴胺能和多巴胺能系统。据报道，胆碱能唤醒系统可能有助于异氟烷、七氟烷、丙泊酚和神经阻滞剂的苏醒。因此，我们集中讨论胆碱能系统在麻醉苏醒中的作用，以及与食欲素能系统的关系。从我们的研究中，我们得到了以下结果。1)在异氟醚麻醉下，大鼠脑室内注射增食欲素可激活脑电图。2)下丘脑后部微量注射谷氨酸通过作用于食欲素神经元诱发脑电觉醒 ...更多信息 urons。3)用食欲素-皂草素选择性破坏外侧下丘脑，可降低异氟醚的最低肺泡浓度。4)异氟烷剂量依赖性地增加了基底前脑中谷氨酸的外排，而不是后下丘脑和皮质中的谷氨酸外排。此外，在异氟烷麻醉下，微量注射AMPA，谷氨酸受体激动剂，剂量依赖性地增加了从皮层的乙酰胆碱（Ach）的流出，这表明异氟烷的麻醉水平可能是平衡的异氟烷的抑制作用和兴奋作用的谷氨酸引起的这种代理。5)在异氟醚麻醉下，基底前脑微量注射食欲素引起Ach流出增加和激活EEG。此外，在异氟醚麻醉下，电刺激脚桥脑被盖（胆碱能上行通路的起源）可增加皮质Ach流出和EEG唤醒。这些作用被选择性食欲素-1受体拮抗剂SB 334867所拮抗。因此，我们认为食欲素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