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Orexin\u2010A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin\u2010A, SB\u2010334867 and TCS\u2010OX2\u201029 (OX<jats:sub>2<\/jats:sub> antagonist). The efficacy of intranasal application of orexin\u2010A versus scopolamine on motion sickness symptoms in cats was also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Orexin\u2010A (i.c.v.) dose\u2010dependently attenuated motion sickness\u2010related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin\u2010A (20\u2009\u03bcg) in rotated animals. Motion sickness responses were differentially inhibited by orexin\u2010A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB\u2010334867 and TCS\u2010OX2\u201029 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin\u2010A. Orexin\u2010A (60\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>) and scopolamine inhibited rotation\u2010induced emesis and non\u2010retching\/vomiting symptoms, while orexin\u2010A also attenuated anorexia with mild salivation in motion sickness cats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Orexin\u2010A might relieve motion sickness through acting on OX<jats:sub>1<\/jats:sub> and OX<jats:sub>2<\/jats:sub> receptors in various hypothalamus nuclei. Intranasal orexin\u2010A could be a potential strategy against motion sickness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16307","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T04:53:43Z","timestamp":1703220823000},"page":"1474-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>Orexin\u2010A<\/scp> attenuated motion sickness through modulating neural activity in hypothalamus nuclei"],"prefix":"10.1111","volume":"181","author":[{"given":"Leilei","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuifeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zichao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruirui","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiling","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Nautical Injury Prevention, Faculty of Navy Medicine Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14091870"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.07.017"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2011.06.015"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn193"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086730"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.08.018"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.01.079"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12225"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.812359"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3878-07.2007"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21604"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01824-7"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2021.113370"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1985.tb02867.x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.015"},{"key":"e_1_2_12_20_1","first-page":"1","article-title":"Intranasal administration of hypocretin 1 (orexin A) bypasses the bloodbrain barrier and targets the brain: A new strategy for the treatment of narcolepsy","volume":"4","author":"Hanson L. 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