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Noradrenaline and orexin levels were measured in the pons, hypothalamus, and cerebral cortex. Ketamine-induced loss-of-righting reflex (LORR) was assessed under modulation of noradrenergic or orexinergic activity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Wild-type rats had higher noradrenaline and orexin levels than transgenic rats across all regions except hypothalamic noradrenaline. Noradrenaline and orexin were correlated in the pons and cortex. Transgenic rats had a shorter LORR duration than wild-type rats (36.3\u2009\u00b1\u200910.4 vs. 46.7\u2009\u00b1\u20095.2\u00a0min, P\u2009=\u20090.002). Noradrenergic activation via intraperitoneal yohimbine prolonged LORR in both genotypes (wild-type: 38.8\u2009\u00b1\u20094.9 vs. 71.9\u2009\u00b1\u200915.3\u00a0min at 3.3\u00a0mg\/kg, P\u2009=\u20090.002; transgenic: 28.1\u2009\u00b1\u20093.9 vs. 71.9\u2009\u00b1\u200924.8\u00a0min, P\u2009&lt;\u20090.001). Noradrenergic deactivation by DSP4 reduced LORR duration (wild-type: 43.3\u2009\u00b1\u20092.18 vs. 36.4\u2009\u00b1\u20096.0\u00a0min, P\u2009=\u20090.005). Intracerebroventricular orexin (1.0\u00a0nmol) shortened LORR (44.0\u2009\u00b1\u200916.7 vs. 30.1\u2009\u00b1\u200915.5\u00a0min, P\u2009=\u20090.001), but co-administration of selective orexin type 1 receptor antagonist YNT-1310 (100\u00a0nmol) counteracted this effect. Notably, orexin or DSP4 reduced LORR duration in wild-type rats but prolonged it in transgenic rats (e.g., wild-type: 40.8\u2009\u00b1\u20096.2 vs. 32.5\u2009\u00b1\u20095.3\u00a0min with orexin, P\u2009=\u20090.0001; transgenic 28.6\u2009\u00b1\u20096.2 vs. 42.1\u2009\u00b1\u20095.6\u00a0min, P\u2009=\u20090.0026).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Orexin-preserved noradrenergic activity supports the typical ketamine-induced sedation profile, highlighting their interactive role in modulating anesthetic depth.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00540-025-03521-x","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T14:33:19Z","timestamp":1749479599000},"page":"710-718","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roles of orexinergic and noradrenergic neuronal activity in ketamine-induced sedation: a study using an orexin-ataxin-3 transgenic rat model"],"prefix":"10.1007","volume":"39","author":[{"given":"Mitsuru","family":"Tonosaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4263-0177","authenticated-orcid":false,"given":"Tetsuya","family":"Kushikata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Nikaido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Takekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyunichi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"3521_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tips.2019.05.001","volume":"40","author":"HC Hemmings Jr","year":"2019","unstructured":"Hemmings HC Jr, Riegelhaupt PM, Kelz MB, Solt K, Eckenhoff RG, Orser BA, Goldstein PA. 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