{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:57:27Z","timestamp":1793120247160,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,10]]},"abstract":"<jats:p>\n                    Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the\n                    <jats:italic>Clock<\/jats:italic>\n                    gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the\n                    <jats:italic>Clock<\/jats:italic>\n                    mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the\n                    <jats:italic>Clock<\/jats:italic>\n                    mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0609625104","type":"journal-article","created":{"date-parts":[[2007,3,22]],"date-time":"2007-03-22T20:18:44Z","timestamp":1174594724000},"page":"6406-6411","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":732,"title":["Mania-like behavior induced by disruption of\n                    <i>CLOCK<\/i>"],"prefix":"10.1073","volume":"104","author":[{"given":"Kole","family":"Roybal","sequence":"first","affiliation":[{"name":"*Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Theobold","sequence":"additional","affiliation":[{"name":"*Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Graham","sequence":"additional","affiliation":[{"name":"*Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"DiNieri","sequence":"additional","affiliation":[{"name":"Behavioral Genetics Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School, MRC 217, 115 Mill Street, Belmont, MA 02478;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Oehrlein","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine Service, Veterans Affairs North Texas Health Care System, 4500 South Lancaster Road, Dallas, TX 75216;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"*Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha H.","family":"Vitaterna","sequence":"additional","affiliation":[{"name":"Center for Functional Genomics and Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208; 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