title: Orexins increase cortical acetylcholine release and electroencephalographic activation through orexin-1 receptor in the rat basal forebrain during isoflurane anesthesia.
abstract: BACKGROUND
  Cholinergic arousal system plays an important role in the maintenance of consciousness. The authors investigated whether the intrabasalis injection of orexin-A or orexin-B and the electrically stimulated pedunculopontine tegmentum nuclei (PPTg: the origin of cholinergic ascending pathways) may alter acetylcholine efflux and electroencephalographic activity in the somatosensory cortex in relation to the orexinergic system in isoflurane-anesthetized rats.
  
  
  METHODS
  Either orexin-A (10, 30, or 100 pmol) or orexin-B (10, 30, or 100 pmol) (n = 6 each) was injected into the basal forebrain while the electroencephalogram was measured during 1.0 minimum alveolar concentration (1.2%) isoflurane anesthesia. Injection of Ringer's solution was used as a control. The PPTg was electrically stimulated twice with the following conditions: 1-s stimulus train (0.2 ms, 100 Hz, 400 microA) per min for 20 min. Twenty minutes before the second PPTg stimulation, Ringer's solution or 20 microg SB334867, an orexin-1 receptor antagonist (n = 5 each) was injected into the basal forebrain.
  
  
  RESULTS
  Injection of orexin-A (30 and 100 pmol) and orexin-B (100 pmol) significantly increased the acetylcholine efflux in the somatosensory cortex (P < 0.05). Injection of orexin-A (10, 30, 100 pmol) and orexin-B (30, 100 pmol) changed the burst and suppression patterns to arousal electroencephalogram. Compared with orexin-B, injection of a lower dose of orexin-A induced increase in the acetylcholine efflux and arousal electroencephalogram. SB334867 significantly attenuated the increases in the acetylcholine efflux and electroencephalographic activation evoked by PPTg stimulation.
  
  
  CONCLUSIONS
  The authors demonstrated that orexin-A was more potent than orexin-B in producing alteration of cholinergic basal forebrain neuronal activity and that the cortical activation induced by the PPTg stimulation against isoflurane anesthesia may be mediated through the orexin-1 receptors in the basal forebrain.
authors.affiliation: Department of Anesthesiology & Reanimatology, Faculty of Medical Science, University of Fukui, Fukui, Japan..
authors.forename: Hai-long
authors.initials: HL
authors.lastname: Dong
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuda
authors.forename: Eri
authors.initials: E
authors.lastname: Murata
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Zhu
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001479:Basal Ganglia / Q000502:physiology; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009287:Naphthyridines; D009479:Neuropeptides / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D018685:Anesthetics, Inhalation; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea; D007530:Isoflurane; D000109:Acetylcholine