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Specifically, while sleepiness is a desirable effect, an orexin antagonist could also produce cataplexy, sudden episodes of muscle weakness often triggered by strong, positive emotions. In this study, we examined the effects of dual orexin receptor antagonists (DORAs), lemborexant (E2006) and almorexant, on sleep\u2013wake behavior and cataplexy during the dark period in wild-type (WT) mice and prepro-orexin knockout (OXKO) mice. In WT mice, lemborexant at 10 and 30 mg\/kg quickly induced NREM sleep in a dose-dependent fashion. In contrast, lemborexant did not alter sleep\u2013wake behavior in OXKO mice. Under the baseline condition, cataplexy was rare in lemborexant-treated WT mice, but when mice were given chocolate as a rewarding stimulus, lemborexant dose-dependently increased cataplexy. Almorexant produced similar results. Collectively, these results demonstrate that DORAs potently increase NREM and REM sleep in mice via blockade of orexin signaling, and higher doses can cause cataplexy when co-administered with a likely rewarding stimulus.<\/jats:p>","DOI":"10.1093\/sleep\/zsz302","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T14:27:15Z","timestamp":1576160835000},"source":"Crossref","is-referenced-by-count":39,"title":["Dual orexin receptor antagonists increase sleep and cataplexy in wild type mice"],"prefix":"10.1093","volume":"43","author":[{"given":"Carrie E","family":"Mahoney","sequence":"first","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Graduate School of Science and Engineering, University of Toyama, Gofuku, 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