title: Effects of orexin-A on propofol anesthesia in rats.
abstract: OBJECTIVE
  An active sleep homeostatic process is present during propofol anesthesia. Activation of the orexin system induces wakefulness, and inhibition of the orexin system causes narcolepsy. We hypothesized that orexin would affect propofol anesthesia.
  
  
  METHODS
  The effects of an intracerebroventricular (i.c.v.) injection of orexin-A (OXA) or an orexin-1 (OX-1) receptor antagonist, SB-334867, on the times to the loss and return of the righting reflex induced by propofol were examined in Wistar rats. The effects of propofol or OXA on norepinephrine (NE) and dopamine (DA) release from the prefrontal cortex (PFC) were examined using in vivo microdialysis.
  
  
  RESULTS
  An i.c.v. injection of OXA (1 nmol) decreased the time to emergence from propofol anesthesia mediated by the OX-1 receptor without changing anesthetic induction (n = 8). An i.c.v. injection of SB-334867 (5 and 50 nmol) increased the time to emergence from propofol anesthesia without changing anesthetic induction (n = 8). Intravenous infusion of propofol decreased NE (48 ± 8%; n = 8) and DA (61.2 ± 11%; n = 8) release from PFC mediated by the GABA(A) receptor. An i.c.v. injection of OXA reversed the decreases in NE and DA release induced by propofol mediated by the OX-1 receptor (n = 8).
  
  
  CONCLUSIONS
  These results indicate that the orexin system may accelerate the emergence from propofol anesthesia associated with increases in the central noradrenergic and dopaminergic activity.
authors.affiliation: Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, 5200 Kihara Kiyotake, Miyazaki 889-1692, Japan. shirasak@med.miyazaki-u.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yonaha
authors.forename: Shin
authors.initials: S
authors.lastname: Onizuka
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuneyoshi
mesh_terms: D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004569:Electroencephalography; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009287:Naphthyridines; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D004856:Postural Balance / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D015742:Propofol; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D012018:Reflex / 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; D018686:Anesthetics, Intravenous; 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; D004298:Dopamine; D009638:Norepinephrine; D015742:Propofol