title: Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse.
abstract: BACKGROUND
  The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing.
  
  
  METHODS
  In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29.
  
  
  RESULTS
  A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels.
  
  
  CONCLUSIONS
  The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness.
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Moore
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
authors.forename: Afaf
authors.initials: A
authors.lastname: Akladious
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Neogene Biosciences LLC, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
authors.forename: Yufen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Case Western Reserve University, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
authors.forename: Sausan
authors.initials: S
authors.lastname: Azzam
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Neogene Biosciences LLC, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
authors.forename: Pingfu
authors.initials: P
authors.lastname: Feng
authors.affiliation: Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Case Western Reserve University, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States. Electronic address: kpstrohl@aol.com.
authors.forename: Kingman P
authors.initials: KP
authors.lastname: Strohl
mesh_terms: D000818:Animals; D001049:Apnea / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002408:Catheters, Indwelling; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004569:Electroencephalography; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000819:agonists* / Q000378:metabolism; D010991:Plethysmography; D017286:Polysomnography; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D012727:Sex Characteristics; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: C572065:1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; C501103:Cd200r1 protein, mouse; D002491:Central Nervous System Agents; D007546:Isoquinolines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D011725:Pyridines
keywords: Mouse model; Orexin 2 agonist; Orexin 2 antagonist; Receptors; Sleep apnea; Sleep disordered breathing