title: Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat.
abstract: OBJECTIVE
  Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.
  
  
  METHODS
  This study used between-groups and within-groups designs.
  
  
  METHODS
  University of Michigan.
  
  
  METHODS
  Adult male Sprague Dawley rats (n = 40).
  
  
  METHODS
  Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.
  
  
  RESULTS
  Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine level. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.
  
  
  CONCLUSIONS
  Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.
authors.affiliation: Neuroscience Program, University of Michigan, Ann Arbor, MI.
authors.forename: Abigail G
authors.initials: AG
authors.lastname: Garrity
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Simhadri
authors.initials: S
authors.lastname: Botta
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Lazar
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Erin
authors.initials: E
authors.lastname: Swor
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Vanini
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI: Neuroscience Program, University of Michigan, Ann Arbor, MI.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Baghdoyan
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI: Neuroscience Program, University of Michigan, Ann Arbor, MI.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D003956:Dialysis; D004569:Electroencephalography; D005786:Gene Expression Regulation / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013377:Substantia Innominata / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D006993:Hypnotics and Sedatives; D016760:Proto-Oncogene Proteins c-fos; D020927:Dexmedetomidine; D000241:Adenosine
keywords: adenosine; anterior hypothalamus; in vivo microdialysis; substantia innominata