{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:47:15Z","timestamp":1787881635691,"version":"build-2784847793"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objectives<\/jats:title>\n                    <jats:p>Trazodone is an antidepressant with robust hypnotic effects, frequently prescribed off-label to treat insomnia. Trazodone has gained recent attention in the context of neurodegenerative diseases because sleep has been proposed as a novel target for disease-modifying therapeutics. Preclinical research in rodents examining the effects of trazodone on sleep is limited, so here we aimed to develop a translationally focused protocol to study the sleep-promoting effects of trazodone in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the effects of voluntary oral trazodone administration at doses of 10, 40, and 60\u00a0mg\/kg on sleep in C57BL\/6J mice (n\u2005=\u200515; females\u2005=\u20056; age 10\u201313 months). Mice were dosed with trazodone for 6 consecutive nights, while being recorded with intracranially implanted 2-channel electroencephalogram (EEG) and electromyography (EMG). EEG\/EMG recordings were analyzed for time spent in each vigilance state and power spectra.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A single dose of trazodone, administered prior to the onset of the 12-h rest phase, dose-dependently increased non-rapid eye movement (NREM) sleep and delta power during NREM sleep, at the expense of rapid eye movement (REM) sleep. These effects on sleep persisted after six consecutive days of dosing, albeit to a lesser extent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have validated a novel voluntary oral administration protocol for trazodone use in mice and have shown that trazodone effectively promotes NREM in mice. Our novel protocol will be useful for future research investigating the effects of trazodone on sleep in mouse models of disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleepadvances\/zpaf031","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T08:05:02Z","timestamp":1746777902000},"source":"Crossref","is-referenced-by-count":3,"title":["The effects of acute trazodone administration on sleep in mice"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9391-4149","authenticated-orcid":false,"given":"Mayuko","family":"Arai","sequence":"first","affiliation":[{"name":"Department of Psychology, Simon Fraser University , Burnaby ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-028X","authenticated-orcid":false,"given":"Brianne A","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Psychology, Simon Fraser University , Burnaby ,","place":["Canada"]},{"name":"Institute for Neuroscience and Neurotechnology, Simon Fraser University , Burnaby ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"issue":"10","key":"2025061607162488600_CIT0001","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1017\/s1092852900024020","article-title":"Mechanism of action of trazodone: a Multifunctional drug","volume":"14","author":"Stahl","year":"2009","journal-title":"CNS Spectr."},{"issue":"12","key":"2025061607162488600_CIT0002","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1517\/14656566.2012.699523","article-title":"Off-label uses of trazodone: a review","volume":"13","author":"Bossini","year":"2012","journal-title":"Expert Opin Pharmacother."},{"issue":"11","key":"2025061607162488600_CIT0003","doi-asserted-by":"publisher","first-page":"e70009","DOI":"10.1002\/gps.70009","article-title":"Real-World use of trazodone in older persons in long term care setting: a retrospective study","volume":"39","author":"Coin","year":"2024","journal-title":"Int J Geriatr Psychiatry."},{"issue":"2","key":"2025061607162488600_CIT0004","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1365-2125.1983.tb04977.x","article-title":"Trazodone enhances sleep in subjective quality but not in objective duration","volume":"16","author":"Montgomery","year":"1983","journal-title":"Br J Clin Pharmacol."},{"issue":"3","key":"2025061607162488600_CIT0005","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/s0924-9338(99)80736-6","article-title":"The effects of trazodone on sleep disturbances induced by brofaromine","volume":"14","author":"Haffmans","year":"1999","journal-title":"Eur Psychiatry"},{"issue":"1","key":"2025061607162488600_CIT0006","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.sleep.2003.06.006","article-title":"The effects of trazodone on sleep in patients treated with stimulant antidepressants","volume":"5","author":"Kaynak","year":"2004","journal-title":"Sleep Med."},{"issue":"4","key":"2025061607162488600_CIT0007","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1097\/01.JCP.0000085411.08426.D3","article-title":"Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations","volume":"23","author":"Le","year":"2003","journal-title":"J Clin Psychopharmacol."},{"issue":"1","key":"2025061607162488600_CIT0008","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1007\/BF00172629","article-title":"Effects of trazodone on the sleep of depressed subjects\u2014a polygraphic study","volume":"95","author":"Mouret","year":"1988","journal-title":"Psychopharmacology (Berl)."},{"issue":"4","key":"2025061607162488600_CIT0009","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1111\/j.1365-2869.2011.00928.x","article-title":"Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs","volume":"20","author":"Roth","year":"2011","journal-title":"J Sleep Res."},{"issue":"2","key":"2025061607162488600_CIT0010","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/s0278-5846(01)00262-7","article-title":"Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone","volume":"26","author":"Saletu-Zyhlarz","year":"2002","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry."},{"issue":"9 SUPPL","key":"2025061607162488600_CIT0011","first-page":"13","article-title":"Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients","volume":"51","author":"Scharf","year":"1990","journal-title":"J Clin Psychiatry."},{"key":"2025061607162488600_CIT0012","doi-asserted-by":"publisher","first-page":"541264","DOI":"10.3389\/FPSYT.2020.00620","article-title":"Effects of trazodone on sleep quality and cognitive function in arteriosclerotic cerebral small vessel disease comorbid with chronic insomnia","volume":"11","author":"Wang","year":"2020","journal-title":"Front Psychiatry."},{"issue":"6156","key":"2025061607162488600_CIT0013","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult brain","volume":"342","author":"Xie","year":"2013","journal-title":"Science."},{"issue":"6465","key":"2025061607162488600_CIT0014","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1126\/science.aax5440","article-title":"Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep","volume":"366","author":"Fultz","year":"2019","journal-title":"Science."},{"issue":"5","key":"2025061607162488600_CIT0015","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1080\/14737175.2024.2341004","article-title":"Pharmacological interventions to improve sleep in people with Alzheimer\u2019s disease: a meta-analysis of randomized controlled trials","volume":"24","author":"Bedward","year":"2024","journal-title":"Expert Rev Neurother."},{"issue":"11","key":"2025061607162488600_CIT0016","doi-asserted-by":"publisher","first-page":"CD009178","DOI":"10.1002\/14651858.CD009178.pub4","article-title":"Pharmacotherapies for sleep disturbances in dementia","volume":"11","author":"McCleery","year":"2020","journal-title":"Cochrane Database Syst Rev."},{"issue":"s1","key":"2025061607162488600_CIT0017","doi-asserted-by":"publisher","first-page":"S205","DOI":"10.3233\/JAD-230635","article-title":"A Randomized-Controlled trial targeting cognition in early Alzheimer\u2019s disease by improving sleep with trazodone (REST)","volume":"101","author":"Eyob","year":"2024","journal-title":"J Alzheimers Dis."},{"issue":"3","key":"2025061607162488600_CIT0018","doi-asserted-by":"publisher","first-page":"911","DOI":"10.3233\/JAD-181145","article-title":"Long-term trazodone use and cognition: a potential therapeutic role for slow-wave sleep enhancers","volume":"67","author":"La","year":"2019","journal-title":"J Alzheimers Dis."},{"issue":"2","key":"2025061607162488600_CIT0019","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/1043-6618(94)80002-2","article-title":"Effects of acute and chronic treatment with trazodone, an antidepressant, on the sleep-wake activity in rats","volume":"30","author":"Lelkes","year":"1994","journal-title":"Pharmacol Res."},{"issue":"16","key":"2025061607162488600_CIT0020","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.1523\/JNEUROSCI.2162-21.2022","article-title":"Improved sleep, memory, and cellular pathological features of tauopathy, including the NLRP3 inflammasome, after chronic administration of trazodone in rTg4510 mice","volume":"42","author":"de Oliveira","year":"2022","journal-title":"J Neurosci."},{"issue":"4","key":"2025061607162488600_CIT0021","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.3233\/JAD-180260","article-title":"Sleep and EEG power spectral analysis in three transgenic mouse models of Alzheimer\u2019s disease: APP\/PS1, 3xTgAD, and Tg2576","volume":"64","author":"Kent","year":"2018","journal-title":"J Alzheimers Dis."},{"key":"2025061607162488600_CIT0022","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.neurobiolaging.2019.01.010","article-title":"Delayed daily activity and reduced NREM slow-wave power in the APPswe\/PS1dE9 mouse model of Alzheimer\u2019s disease","volume":"78","author":"Kent","year":"2019","journal-title":"Neurobiol Aging."},{"issue":"4","key":"2025061607162488600_CIT0023","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/BF02245272","article-title":"Effects of trazodone on EEG sleep and clinical state in major depression","volume":"107","author":"van Bemmel","year":"1992","journal-title":"Psychopharmacology (Berl)."}],"container-title":["Sleep Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/sleepadvances\/advance-article-pdf\/doi\/10.1093\/sleepadvances\/zpaf031\/63384903\/zpaf031.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleepadvances\/article-pdf\/6\/2\/zpaf031\/63384903\/zpaf031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleepadvances\/article-pdf\/6\/2\/zpaf031\/63384903\/zpaf031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T07:16:35Z","timestamp":1750058195000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/sleepadvances\/article\/doi\/10.1093\/sleepadvances\/zpaf031\/8151807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4,10]]}},"URL":"https:\/\/doi.org\/10.1093\/sleepadvances\/zpaf031","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.22.634422","asserted-by":"object"}]},"ISSN":["2632-5012"],"issn-type":[{"value":"2632-5012","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,4]]},"article-number":"zpaf031"}}