title: Involvement of tuberomamillary histaminergic neurons in isoflurane anesthesia.
abstract: BACKGROUND
  The brain histaminergic system plays a critical role in maintenance of arousal. Previous studies suggest that histaminergic neurotransmission might be a potential mediator of general anesthetic actions. However, it is not clear whether histaminergic tuberomamillary nucleus (TMN) is necessarily involved in the sedative/hypnotic effects of general anesthetics.
  
  
  METHODS
  Male Long Evans rats underwent either TMN orexin-saporin/sham lesion or implantation of intracerebroventricular cannula 2 weeks before the experiment. The behavioral endpoint of loss of righting reflex was used to assess the hypnotic property of isoflurane, propofol, pentobarbital, and ketamine in animals. Histaminergic cell loss was assessed by adenosine deaminase expression in the TMN using immunohistochemistry.
  
  
  RESULTS
  Rats with bilateral TMN orexin-saporin lesion induced an average 72% loss of histaminergic cells compared with sham-lesion rats. TMN orexin-saporin lesion or intracerebroventricular administration of triprolidine (an H1 receptor antagonist) decreased the 50% effective concentration for loss of righting reflex value and prolonged emergence time to isoflurane anesthesia. However, TMN orexin-saporin lesion had no significant effect on the anesthetic sensitivity to propofol, pentobarbital, and ketamine.
  
  
  CONCLUSIONS
  These findings suggest a role of the TMN histaminergic neurons in modulating isoflurane anesthesia and that the neural circuits for isoflurane-induced hypnosis may differ from those of γ-aminobutyric acid-mediated anesthetics and ketamine.
authors.affiliation: Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: L Stan
authors.initials: LS
authors.lastname: Leung
mesh_terms: D000769:Anesthesia, Inhalation; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists; D007034:Hypothalamus, Posterior / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007530:Isoflurane; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology*; D064446:Orexin Receptors; D010424:Pentobarbital / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins
chemical_list: D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D006633:Histamine Antagonists; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D054789:Ribosome Inactivating Proteins, Type 1; D007649:Ketamine; D006632:Histamine; D007530:Isoflurane; D000076985:Saporins; D010424:Pentobarbital; D015742:Propofol