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      Effect of suvorexant on event-related oscillations and EEG sleep in rats exposed to chronic intermittent ethanol vapor and protracted withdrawal

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          Abstract

          Study Objectives

          Insomnia is a prominent complaint in patients with alcohol use disorders (AUD). However, despite the importance of sleep in the maintenance of sobriety, treatment options for sleep disturbance associated with a history of AUD are currently limited. Recent clinical trials have demonstrated that suvorexant, a dual Hct/OX receptor antagonist, normalizes sleep in patients with primary insomnia; yet, its potential for the treatment of sleep pathology associated with AUD has not been investigated in either preclinical or clinical studies.

          Methods

          This study employed a model whereby ethanol vapor exposure or control conditions were administered for 8 weeks to adult rats. Waking event-related oscillations (EROs) and EEG sleep were evaluated at baseline before exposure and again following 24 hr of withdrawal from the exposure. Subsequently, the ability of vehicle (VEH) and two doses (10, 30 mg/kg IP) of suvorexant to modify EROs, sleep, and the sleep EEG was investigated.

          Results

          After 24 hr following EtOH withdrawal, the ethanol-treated group had increases in waking ERO θ and β activity, more fragmented sleep (shorter duration and increased frequency of slow wave (SW) and rapid eye movement [REM] sleep episodes), and increased θ and β power in REM and SW sleep. Suvorexant induced a dose-dependent decrease in the latency to REM and SW sleep onsets but also produced REM and SW sleep fragmentation and increased β energy in waking EROs when compared with VEH.

          Conclusions

          Taken together, these studies suggest that suvorexant has overall sleep-promoting effects, but it may exacerbate some aspects of sleep and EEG pathology.

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          Author and article information

          Journal
          Sleep
          Sleep
          sleep
          Sleep
          Oxford University Press (US )
          0161-8105
          1550-9109
          April 2019
          31 January 2019
          31 January 2020
          : 42
          : 4
          : zsz020
          Affiliations
          Department of Neurosciences, The Scripps Research Institute, La Jolla, CA
          Author notes
          Corresponding author. Cindy L. Ehlers, Department of Neurosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Email: cindye@ 123456scripps.edu
          Author information
          http://orcid.org/0000-0002-8164-8452
          http://orcid.org/0000-0002-2717-994X
          Article
          PMC6448295 PMC6448295 6448295 zsz020
          10.1093/sleep/zsz020
          6448295
          30715515
          4d8af019-5dae-444b-9000-589513688691
          © Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

          This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

          History
          : 21 September 2018
          : 07 December 2018
          Page count
          Pages: 14
          Funding
          Funded by: National Institutes of Health 10.13039/100000002
          Award ID: U01 AA019969
          Award ID: R01 AA006059
          Funded by: National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027
          Categories
          Basic Science of Sleep and Circadian Rhythms

          event-related oscillations,suvorexant,EEG,slow-wave sleep,alcohol

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