Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of sprague dawley rat

Elizabeth A. Gauthier, Sarah E. Guzick, Chad M. Brummett, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)743-753
Number of pages11
JournalAnesthesiology
Volume115
Issue number4
DOIs
StatePublished - Jan 1 2011

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Buprenorphine
Adenosine
Sprague Dawley Rats
Sleep
Brain
Substantia Innominata
Eye Movements
Wakefulness
Hypnotics and Sedatives
Opioid Analgesics
Indwelling Catheters
Narcotic Antagonists
REM Sleep
Microdialysis
Opioid Receptors
Intravenous Administration
Brain Stem
Analgesics

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of sprague dawley rat. / Gauthier, Elizabeth A.; Guzick, Sarah E.; Brummett, Chad M.; Baghdoyan, Helen; Lydic, Ralph.

In: Anesthesiology, Vol. 115, No. 4, 01.01.2011, p. 743-753.

Research output: Contribution to journalArticle

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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.",
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AU - Baghdoyan, Helen

AU - Lydic, Ralph

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