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

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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