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Rep"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Serotonin (5-HT) 5-HT<jats:sub>2C<\/jats:sub>receptor mRNA editing (at five sites, A\u2013E), implicated in neuropsychiatric disorders, including clinical depression, remains unexplored during alcohol abstinence\u2014often accompanied by depressive symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used deep sequencing to investigate 5-HT<jats:sub>2C<\/jats:sub>receptor editing in mice during early ethanol deprivation following prolonged alcohol exposure and mice lacking tryptophan hydroxylase (TPH)2, a key enzyme in central 5-HT production. We also examined<jats:italic>Tph2<\/jats:italic>expression in ethanol-deprived animals using quantitative real-time PCR (qPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cessation from chronic 10% ethanol exposure in a two-bottle choice paradigm enhanced immobility time and decreased latency in the forced swim test (FST), indicating a depression-like phenotype. In the hippocampus, ethanol-deprived \u201chigh ethanol-drinking\u201d mice displayed reduced<jats:italic>Tph2<\/jats:italic>expression, elevated 5-HT<jats:sub>2C<\/jats:sub>receptor editing efficiency, and decreased frequency of the D mRNA variant, encoding the less-edited INV protein isoform.<jats:italic>Tph2<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>mice showed attenuated receptor editing in the hippocampus and elevated frequency of non-edited None and D variants. In the prefrontal cortex,<jats:italic>Tph2<\/jats:italic>deficiency increased receptor mRNA editing at site D and reduced the frequency of AB transcript, predicting a reduction in the corresponding partially edited VNI isoform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings reveal differential effects of 5-HT depletion and ethanol cessation on 5-HT<jats:sub>2C<\/jats:sub>receptor editing. Central 5-HT depletion attenuated editing in the prefrontal cortex and the hippocampus, whereas ethanol deprivation, coinciding with reduced<jats:italic>Tph2<\/jats:italic>expression in the hippocampus, enhanced receptor editing efficiency specifically in this brain region. This study highlights the interplay between 5-HT synthesis, ethanol cessation, and 5-HT<jats:sub>2C<\/jats:sub>receptor editing, providing potential mechanism underlying increased ethanol consumption and deprivation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical abstract<\/jats:title><\/jats:sec>","DOI":"10.1007\/s43440-023-00545-6","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T17:02:16Z","timestamp":1699030936000},"page":"1502-1521","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ethanol deprivation and central 5-HT deficiency differentially affect the mRNA editing of the 5-HT2C receptor in the mouse brain"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9716-6661","authenticated-orcid":false,"given":"Magdalena","family":"Zaniewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Fr\u00f6hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"545_CR1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1126\/science.1078197","volume":"299","author":"DJ Walther","year":"2003","unstructured":"Walther DJ, Peter JU, Bashammakh S, H\u00f6rtnagl H, Voits M, Fink H, et al. 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