{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:07:49Z","timestamp":1788797269648,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Post-traumatic stress disorder (PTSD) is characterized by symptoms including hypervigilance, intrusive memories, and sleep disturbance. Insomnia and nightmares are among the most common and clinically important sleep-related symptoms in PTSD, yet effective and well-tolerated pharmacotherapies remain limited. Suvorexant, a dual orexin receptor antagonist (DORA) approved for insomnia, represents a mechanistically distinct approach to traditional hypnotics. The orexin\/hypocretin system is composed of two wake-promoting neuropeptides, orexin A and orexin B, which signal through orexin 1 (OX\n                    <jats:sub>1<\/jats:sub>\n                    R) and orexin 2 receptors (OX\n                    <jats:sub>2<\/jats:sub>\n                    R) to regulate arousal and sleep\u2013wake transitions. The adaptive stress response, which is canonically disrupted in PTSD, is also moderated by the orexin system. Here, we used an acute inescapable footshock paradigm to disrupt sleep in adult male Sprague Dawley rats and evaluated whether orexin receptor antagonism restores sleep after stress. Systemic administration of a dual orexin receptor antagonist (suvorexant), an OX\n                    <jats:sub>1<\/jats:sub>\n                    R-preferring antagonist (SB334867), and an OX\n                    <jats:sub>2<\/jats:sub>\n                    R-selective antagonist (EMPA), partially restored REM sleep and attenuated increases in NREM sleep following footshock stress exposure. We also examined the relative contribution of OX\n                    <jats:sub>1<\/jats:sub>\n                    R and OX\n                    <jats:sub>2<\/jats:sub>\n                    R to these effects at the doses used. Although all antagonists increased time spent in REM after footshock stress, attenuation of the stress-induced increases in NREM and reductions in sleep-onset latency were most evident following dual receptor blockade. These findings demonstrate that orexin receptor antagonism can mitigate acute stress-induced alterations in sleep state allocation and sleep latency, and support further investigation of DORAs for stress-related sleep disturbance.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1898419","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:01Z","timestamp":1788793801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Orexin receptor antagonists attenuate acute stress-induced disruptions in sleep states"],"prefix":"10.3389","volume":"20","author":[{"given":"Kayla","family":"Lilly","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, UT Health San Antonio","place":["San Antonio, TX, United States"]},{"name":"South Texas Veterans Health Care System, Audie L. Murphy Division","place":["San Antonio, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, UT Health San Antonio","place":["San Antonio, TX, United States"]},{"name":"South Texas Veterans Health Care System, Audie L. Murphy Division","place":["San Antonio, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Lodge","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, UT Health San Antonio","place":["San Antonio, TX, United States"]},{"name":"South Texas Veterans Health Care System, Audie L. Murphy Division","place":["San Antonio, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/nm1544","article-title":"Promotion of sleep by targeting the orexin system in rats, dogs and humans","volume":"13","author":"Brisbare-Roch","year":"2007","journal-title":"Nat. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s40501-020-00222-y","article-title":"Treatment of sleep comorbidities in posttraumatic stress disorder","volume":"7","author":"Brownlow","year":"2020","journal-title":"Curr. Treat. 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