title: Ketamine and propofol have opposite effects on postanesthetic sleep architecture in rats: relevance to the endogenous sleep-wakefulness substances orexin and melanin-concentrating hormone.
abstract: Anesthesia and surgery disturb sleep. Disturbed sleep adversely affects postoperative complications involving the cardiovascular system, diabetes, and infection. General anesthetics share neuronal mechanisms involving endogenous sleep-wakefulness-related substances, such as orexin (OX) and melanin-concentrating hormone (MCH). We evaluated changes in sleep architecture and the concentration of OX and MCH during the peri-anesthetic period.
  
  
  
  To examine sleep architecture, male Sprague-Dawley rats weighing 350-450 g received ketamine 100 mg/kg (n = 9) or propofol 80 mg/kg (n = 6) by intraperitoneal injection. Electroencephalography was recorded from 2 days pre- to 5 days postanesthesia. To quantify levels of OX and MCH, 144 similar rats received the same doses of ketamine (n = 80) or propofol (n = 64). Brain concentrations of these substances were determined at 0, 20, 60, and 120 min after anesthetic administration.
  
  
  
  Ketamine decreased OX content in the hypothalamus during the anesthesia period. OX content was restored to pre-anesthesia levels in the hypothalamus and pons. Both anesthetics increased brain MCH content in the postanesthetic period, with the degree of increase being greater with propofol. Ketamine enhanced wakefulness and inhibited non-rapid eye movement sleep (NREMS) immediately after anesthesia. Conversely, propofol inhibited wakefulness and enhanced NREMS in that period. Ketamine inhibited wakefulness and enhanced NREMS during the dark phase on the first postanesthesia day.
  
  
  
  Anesthetics affect various endogenous sleep-wakefulness-related substances; however, the modulation pattern may depend on the type of anesthetic. The process of postanesthetic sleep disturbance was agent specific. Our results provide fundamental evidence to treat anesthetic-related sleep disturbance.
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan. tetsuyak@hirosaki-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
authors.affiliation: Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, 036-8563, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sawada
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Niwa
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, 036-8563, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tonosaki
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
mesh_terms: D000758:Anesthesia; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004569:Electroencephalography; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D007028:Hypothalamic Hormones; D008543:Melanins; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D007649:Ketamine; D015742:Propofol
keywords: Ketamine; Melanin-concentrating hormone; Orexin; Propofol; Sleep; Sleep disturbance