[Role of orexin in the cholinergic ascending arousal system--orexin-induced arousal from anesthesia].

The cholinergic ascending arousal pathway is one of the most powerful cortical activation systems. The origins of this system is from the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDT), which relay their signals to the posterior hypothalamus, the basal forebrain and then the cerebral cortex. The cholinergic activation by selective agonists or cholinesterase inhibitors has been shown to produce cortical activation and induce awareness from anesthesia. Orexin neurons are localized in the lateral to posterior hypothalamus. In this review, we presented the antagonistic action of orexin-A to isoflurane anesthesia in terms of the cortical release of acetylcholine and EEG arousal. Microinjection of orexin-A into the basal forebrain induced the increases in acetylcholine release and EEG arousal through orexin-1 receptors. Furthermore, electrical stimulation of the PPTg induced the increases in acetylcholine release and EEG arousal under isoflurane anesthesia, and SB334867, an orexin-1 receptor antagonist, attenuated these arousal responses. These findings suggest that the orexinergic system may contribute to the arousal from anesthesia through the cholinergic ascending arousal pathway.