Document Detail


Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat.
MedLine Citation:
PMID:  21857500     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Elizabeth A Gauthier; Sarah E Guzick; Chad M Brummett; Helen A Baghdoyan; Ralph Lydic
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  115     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-22     Completed Date:  2011-11-15     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  743-53     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine / metabolism*
Analgesics, Opioid / pharmacology*
Animals
Azabicyclo Compounds / pharmacology
Behavior, Animal / drug effects
Brain Chemistry / drug effects*
Buprenorphine / pharmacology*
Delta Rhythm / drug effects
Electroencephalography / drug effects
Hypnotics and Sedatives / pharmacology
Male
Microdialysis
Pain Measurement / drug effects
Piperazines / pharmacology
Polysomnography / drug effects
Pons / drug effects,  metabolism
Rats
Rats, Sprague-Dawley
Reticular Formation / drug effects,  metabolism
Sleep / drug effects*,  physiology*
Substantia Innominata / drug effects,  metabolism
Wakefulness / drug effects
Grant Support
ID/Acronym/Agency:
HL40881/HL/NHLBI NIH HHS; HL65272/HL/NHLBI NIH HHS; L30 GM094967-01/GM/NIGMS NIH HHS; MH45361/MH/NIMH NIH HHS; R01 HL040881/HL/NHLBI NIH HHS; R01 HL040881-21/HL/NHLBI NIH HHS; R01 HL065272/HL/NHLBI NIH HHS; R01 HL065272-11/HL/NHLBI NIH HHS; R37 MH045361/MH/NIMH NIH HHS; R37 MH045361-25/MH/NIMH NIH HHS; UL1RR024986/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Opioid; 0/Azabicyclo Compounds; 0/Hypnotics and Sedatives; 0/Piperazines; 0/eszopiclone; 40D3SCR4GZ/Buprenorphine; K72T3FS567/Adenosine
Comments/Corrections

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