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Serotonin modulates the circadian effects of light, with agonists inhibiting response to light and antagonists enhancing responses to light. A special class of serotonergic compounds, the mixed 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub> agonist\/antagonists, potentiates light\u2010induced phase advances by up to 400% when administered acutely. In this study, we examine the effects of one of these mixed 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub> agonist\/antagonists, <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378, when administered chronically. Thirty adult male hamsters were administered either vehicle or <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 via surgically implanted osmotic mini pumps over a period of 28\u00a0days. In a light\u00a0:\u00a0dark cycle, chronic <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 advanced the phase angle of entrainment, prolonged the duration of the active phase and attenuated the amplitude of the wheel\u2010running rhythm during the early night. In constant darkness, chronic treatment with <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 significantly attenuated light\u2010induced phase advances, but had no significant effect on light\u2010induced phase delays. Non\u2010photic phase shifts to daytime administration of a 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A\/7<\/jats:sub> agonist were also attenuated by chronic <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 treatment. <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analysis revealed that chronic <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 treatment upregulated <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub> and 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1B<\/jats:sub> receptors in the hypothalamus and downregulated <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub> and monoamine oxidase\u2010A in the brainstem. These results highlight adaptive changes of serotonin receptors in the brain to chronic treatment with <jats:styled-content style=\"fixed-case\">BMY<\/jats:styled-content>7378 and link such up\u2010 and downregulation to changes in important circadian parameters. Such long\u2010term changes to the circadian system should be considered when patients are treated chronically with drugs that alter serotonergic function.<\/jats:p>","DOI":"10.1111\/ejn.13744","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T07:56:41Z","timestamp":1508227001000},"page":"2782-2790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic <scp>BMY<\/scp>7378 treatment alters behavioral circadian rhythms"],"prefix":"10.1111","volume":"46","author":[{"given":"Jhenkruthi","family":"Vijaya Shankara","sequence":"first","affiliation":[{"name":"Department of Psychology University of Calgary 2500 University Drive NW Calgary AB T2N 1N4 Canada"},{"name":"Hotchkiss Brain Institute University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang\u00e9lique","family":"Orr","sequence":"additional","affiliation":[{"name":"Department 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