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Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro\u2010amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14\u00a0days of dextro\u2010amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro\u2010amphetamine injections. Adult C57BL\/6 mice received 7\u00a0days of valproate or sodium butyrate administration, being sleep deprived at the last 36\u00a0hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open\u2010field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro\u2010amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment.<\/jats:p>","DOI":"10.1111\/ejn.14922","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T14:03:51Z","timestamp":1596204231000},"page":"649-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-5904","authenticated-orcid":false,"given":"Roger B","family":"Varela","sequence":"first","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC) Crici\u00fama Brazil"},{"name":"Queensland Brain Institute The University of Queensland Brisbane QLD 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