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Conventional therapy takes weeks to months to improve symptoms. Ketamine has rapid onset antidepressant effects. Yet its action on HPA axis activity is poorly understood. Here, we measured the corticosterone (CORT) response to ketamine administered at different times of day in the Wistar\u2013Kyoto (WKY) rat. In male rats, blood was collected every 10\u00a0min for 28\u2009h using an automated blood sampling system. Ketamine (5\/10\/25\u2009mg\u2009\u00b7\u2009kg) was infused through a subcutaneous cannula at two time points\u2013during the active and inactive period. CORT levels in blood were measured in response to ketamine using a radioimmunoassay. WKY rats displayed robust circadian secretion of corticosterone and was not overly different to Sprague Dawley rats. Ketamine (all doses) significantly increased CORT response at both infusion times. However, a dose dependent effect and marked increase over baseline was observed when ketamine was administered during the inactive phase. Ketamine has a robust and rapid effect on HPA axis function. The timing of ketamine injection may prove crucial for glucocorticoid\u2010mediated action in depression.<\/jats:p>","DOI":"10.1111\/jne.13194","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T07:29:35Z","timestamp":1659857375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Time of day influences stress hormone response to ketamine"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3964-5247","authenticated-orcid":false,"given":"Matthew T.","family":"Birnie","sequence":"first","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroendocrinology, School of Medicine University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alen V.","family":"Eapen","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroendocrinology, School of Medicine 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