title: The effects of benzodiazepines on orexinergic systems in rat cerebrocortical slices.
abstract: BACKGROUND
  As orexinergic (OXergic) neurons have been reported to mediate emotional changes, benzodiazepines might interact with OXergic neurons.
  
  
  METHODS
  We examined the interactions between OXergic neurons and benzodiazepine receptors in orexin-A (100 nM) and K+ (25 mM)-evoked norepinephrine release from rat cerebrocortical slices.
  
  
  RESULTS
  Midazolam, diazepam, and flunitrazepam concentration-dependently inhibited both OX-A- and K+-evoked norepinephrine release. The IC50 of midazolam for orexin-A-evoked release (0.87 microM, P < 0.01), which was insensitive to flumazenil, was significantly lower than that of diazepam and flunitrazepam (around 60 microM), whereas the IC50s for K+-evoked release were not different among the benzodiazepines.
  
  
  CONCLUSIONS
  There may be no interaction between OXergic neurons and central benzodiazepine receptors.
authors.affiliation: Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kudo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kudo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
authors.forename: Enyou
authors.initials: E
authors.lastname: Li
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D008874:Midazolam; D009638:Norepinephrine