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Herein, we studied the transcriptional regulation of the endocannabinoid system, an interesting target for body weight maintenance and the control of food intake and energy balance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We used two well\u2010characterized animal models of AN: (a) the activity\u2010based anorexia (ABA) model in which rats, housed with running wheels and subjected to daily food restriction, show reductions in body weight and increase in physical activity; (b) the genetic anx\/anx mouse displaying the core features of AN: low food intake and emaciation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the evaluated endocannabinoid system components, we observed a selective and significant down\u2010regulation of the gene encoding for the type 1 cannabinoid receptor (<jats:italic>Cnr1<\/jats:italic>) in ABA rats' hypothalamus and nucleus accumbens and, in the latter area, a consistent, significant and correlated increase in DNA methylation at the gene promoter. No changes were evident in the anx\/anx mice except for a down\u2010regulation of <jats:italic>Cnr1<\/jats:italic>, in the prefrontal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings support a possible role for <jats:italic>Cnr1<\/jats:italic> in the ABA animal model of AN. In particular, its regulation in the nucleus accumbens appears to be triggered by environmental cues due to the consistent epigenetic modulation of the promoter. These data warrant further studies on <jats:italic>Cnr1<\/jats:italic> regulation as a possible target for treatment of AN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/eat.23271","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T10:45:30Z","timestamp":1586515530000},"page":"702-716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Epigenetic regulation of the cannabinoid receptor <scp>CB1<\/scp> in an activity\u2010based rat model of anorexia nervosa"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-098X","authenticated-orcid":false,"given":"Claudio","family":"D'Addario","sequence":"first","affiliation":[{"name":"Faculty of Bioscience and Technology for Food, Agriculture and Environment University of Teramo  Teramo Italy"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm 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