Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat

Overview

Journal Anesthesiology

Specialty Anesthesiology

Date 2011 Aug 23

PMID 21857500

Citations 23

Authors

Elizabeth A Gauthier

Sarah E Guzick

Chad M Brummett

Helen A Baghdoyan

Ralph Lydic

Affiliations

Soon will be listed here.

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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References

Keifer J, Baghdoyan H, Lydic R . Sleep disruption and increased apneas after pontine microinjection of morphine. Anesthesiology. 1992; 77(5):973-82. DOI: 10.1097/00000542-199211000-00021. View

Tanase D, Martin W, Baghdoyan H, Lydic R . G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a mu opioid and an adenosine A1 receptor agonist. Sleep. 2001; 24(1):52-62. DOI: 10.1093/sleep/24.1.52. View

Kalinchuk A, Urrila A, Alanko L, Heiskanen S, Wigren H, Suomela M . Local energy depletion in the basal forebrain increases sleep. Eur J Neurosci. 2003; 17(4):863-9. DOI: 10.1046/j.1460-9568.2003.02532.x. View

Watson C, Soto-Calderon H, Lydic R, Baghdoyan H . Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness. Sleep. 2008; 31(4):453-64. PMC: 2279760. DOI: 10.1093/sleep/31.4.453. View

Kundermann B, Krieg J, Schreiber W, Lautenbacher S . The effect of sleep deprivation on pain. Pain Res Manag. 2004; 9(1):25-32. DOI: 10.1155/2004/949187. View

Lavigne G . Effect of sleep restriction on pain perception: towards greater attention!. Pain. 2009; 148(1):6-7. DOI: 10.1016/j.pain.2009.10.013. View

Porkka-Heiskanen T, Alanko L, Kalinchuk A, Stenberg D . Adenosine and sleep. Sleep Med Rev. 2003; 6(4):321-32. DOI: 10.1053/smrv.2001.0201. View

Watson C, Lydic R, Baghdoyan H . Sleep and GABA levels in the oral part of rat pontine reticular formation are decreased by local and systemic administration of morphine. Neuroscience. 2006; 144(1):375-86. PMC: 2729685. DOI: 10.1016/j.neuroscience.2006.09.007. View

Furlan A, Sandoval J, Mailis-Gagnon A, Tunks E . Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006; 174(11):1589-94. PMC: 1459894. DOI: 10.1503/cmaj.051528. View

10.

Nelson A, Battersby A, Baghdoyan H, Lydic R . Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology. 2009; 111(6):1327-33. PMC: 2784661. DOI: 10.1097/ALN.0b013e3181bdf894. View

11.

Van Dort C, Baghdoyan H, Lydic R . Adenosine A(1) and A(2A) receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci. 2009; 29(3):871-81. PMC: 3430130. DOI: 10.1523/JNEUROSCI.4111-08.2009. View

12.

Chhangani B, Roehrs T, Harris E, Hyde M, Drake C, Hudgel D . Pain sensitivity in sleepy pain-free normals. Sleep. 2009; 32(8):1011-7. PMC: 2717191. View

13.

Wang W, Baghdoyan H, Lydic R . Leptin replacement restores supraspinal cholinergic antinociception in leptin-deficient obese mice. J Pain. 2009; 10(8):836-43. PMC: 2777714. DOI: 10.1016/j.jpain.2009.02.003. View

14.

Gan T, Habib A . Adenosine as a non-opioid analgesic in the perioperative setting. Anesth Analg. 2007; 105(2):487-94. DOI: 10.1213/01.ane.0000267260.00384.d9. View

15.

Feinberg I, Floyd T, March J . Effects of sleep loss on delta (0.3-3 Hz) EEG and eye movement density: new observations and hypotheses. Electroencephalogr Clin Neurophysiol. 1987; 67(3):217-21. DOI: 10.1016/0013-4694(87)90019-8. View

16.

Van Dongen H, Maislin G, Mullington J, Dinges D . The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003; 26(2):117-26. DOI: 10.1093/sleep/26.2.117. View

17.

Zhu Z, Bowman H, Baghdoyan H, Lydic R . Morphine increases acetylcholine release in the trigeminal nuclear complex. Sleep. 2008; 31(12):1629-37. PMC: 2603485. DOI: 10.1093/sleep/31.12.1629. View

18.

Porkka-Heiskanen T, Strecker R, Thakkar M, Bjorkum A, Greene R, McCarley R . Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science. 1997; 276(5316):1265-8. PMC: 3599777. DOI: 10.1126/science.276.5316.1265. View

19.

Karlsson M, Berggren A . Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, open-label,.... Clin Ther. 2009; 31(3):503-13. DOI: 10.1016/j.clinthera.2009.03.001. View

20.

Orman J, Keating G . Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence. Drugs. 2009; 69(5):577-607. DOI: 10.2165/00003495-200969050-00006. View