title: Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat.
abstract: BACKGROUND
  Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine concentrations in regions of the basal forebrain and pontine brainstem that regulate sleep.
  
  
  METHODS
  Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep-wake states were recorded for 24 h. In additional rats, buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while adenosine was simultaneously measured.
  
  
  RESULTS
  An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in nonrapid eye movement sleep (-22.1%) and rapid eye movement sleep (-3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative-hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine concentrations in the pontine reticular formation (-14.6%) and substantia innominata (-36.7%). Intravenous administration of buprenorphine significantly decreased (-20%) adenosine in the substantia innominata.
  
  
  CONCLUSIONS
  Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative-hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine concentrations in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gauthier
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Guzick
authors.forename: Chad M
authors.initials: CM
authors.lastname: Brummett
authors.forename: Helen A
authors.initials: HA
authors.lastname: Baghdoyan
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D053961:Azabicyclo Compounds / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002047:Buprenorphine / Q000494:pharmacology*; D003700:Delta Rhythm / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D000069582:Eszopiclone; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D017286:Polysomnography / Q000187:drug effects; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D013377:Substantia Innominata / Q000187:drug effects / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D002047:Buprenorphine; D000241:Adenosine; D000069582:Eszopiclone