{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:18:45Z","timestamp":1768479525225,"version":"3.49.0"},"reference-count":106,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"publisher","award":["Neurotime Erasmus Mundus + program of the European Commission"],"award-info":[{"award-number":["Neurotime Erasmus Mundus + program of the European Commission"]}],"id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The circadian system interacts with the mesocorticolimbic reward system to modulate reward and memory in a time-of-day dependent manner. The circadian discrimination of reward, however, remains difficult to address between natural reinforcers and drugs of abuse. Circadian rhythms control cocaine sensitization and conversely cocaine causes long-term alteration in circadian periodicity in part through the serotonergic neurotransmission. Since neural circuits activated by cocaine and natural reinforcers do not completely overlap, we compared the effect of cocaine with that of sucrose, a strong reinforcer in rodents, by using passive chronic administration. The expression of fifteen genes playing a major role in DNA methylation (Dnmts, Tets), circadian rhythms (Clock, Bmal1, Per1\/2, Cry1\/2, Rev-Erb\u03b2, Dbp1), appetite, and satiety (Orexin, Npy) was analyzed in dopamine projection areas like the prefrontal cortex, the caudate putamen, and the hypothalamus interconnected with the reward system. The corresponding proteins of two genes (Orexin, Per2) were examined by IHC. For many factors controlling biological and cognitive functions, striking opposite responses were found between the two reinforcers, notably for genes controlling DNA methylation\/demethylation processes and in global DNA methylation involved in chromatin remodeling. The data are consistent with a repression of critical core-clock genes by cocaine, suggesting that, consequently, both agents differentially modulate day\/night cycles. Whether observed cocaine and sucrose-induced changes in DNA methylation in a time dependent manner are long lasting or contribute to the establishment of addiction requires further neuroepigenetic investigation. Understanding the mechanisms dissociating drugs of abuse from natural reinforcers remains a prerequisite for the design of selective therapeutic tools for compulsive behaviors.<\/jats:p>","DOI":"10.3390\/genes12081195","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Rhythmic Regulation of DNA Methylation Factors and Core-Clock Genes in Brain Structures Activated by Cocaine or Sucrose: Potential Role of Chromatin Remodeling"],"prefix":"10.3390","volume":"12","author":[{"given":"Lamis","family":"Saad","sequence":"first","affiliation":[{"name":"Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS, Universit\u00e9 de Strasbourg, Neurop\u00f4le de Strasbourg, 67000 Strasbourg, France"},{"name":"The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, 1066 EA Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-8453","authenticated-orcid":false,"given":"Andries","family":"Kalsbeek","sequence":"additional","affiliation":[{"name":"The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, 1066 EA Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Zwiller","sequence":"additional","affiliation":[{"name":"Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS, Universit\u00e9 de Strasbourg, Neurop\u00f4le de Strasbourg, 67000 Strasbourg, France"},{"name":"CNRS, Centre National de la Recherche Scientifique, 75016 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-441X","authenticated-orcid":false,"given":"Patrick","family":"Anglard","sequence":"additional","affiliation":[{"name":"Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS, Universit\u00e9 de Strasbourg, Neurop\u00f4le de Strasbourg, 67000 Strasbourg, France"},{"name":"INSERM, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.neuroimage.2012.05.076","article-title":"fMRI response in the medial prefrontal cortex predicts cocaine but not sucrose self-administration history","volume":"62","author":"Lu","year":"2012","journal-title":"Neuroimage"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14179","DOI":"10.1523\/JNEUROSCI.4477-07.2007","article-title":"Repeated electrical stimulation of reward-related brain regions affects cocaine but not \u201cnatural\u201d reinforcement","volume":"27","author":"Levy","year":"2007","journal-title":"J. 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