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Glycogen synthase kinase 3\u2010beta (GSK3\u03b2) has been implicated in ethanol behaviours and poses as a potential therapeutic target in the treatment of AUD. Here, we investigated the preclinical evidence for tideglusib, a clinically available selective GSK3\u03b2 inhibitor, in modulating chronic and binge ethanol consumption. Tideglusib decreased ethanol consumption in both a model of daily, progressive ethanol intake (two\u2010bottle choice, intermittent ethanol access) and binge\u2010like drinking behaviour (drinking in the dark) without effecting water intake. With drinking in the dark, tideglusib was more potent in males (ED50\u2009=\u200964.6, CI\u2009=\u200958.9\u201370.8) than females (ED50\u2009=\u200979.4, CI\u2009=\u200970.8\u201393.3). Further, we found tideglusib had no effect on ethanol pharmacokinetics, taste preference or anxiety\u2010like behaviour, although there was a transient increase in total locomotion following treatment. Additionally, tideglusib treatment did not alter liver function as measured by serum activity of alanine aminotransferase and aspartate aminotransferase but did cause a decrease in serum alkaline phosphatase activity. RNA sequencing analysis of tideglusib actions on ethanol consumption revealed alterations in genes involved in synaptic plasticity and transmission, as well as genes downstream of the canonical Wnt signalling pathway, suggesting tideglusib may modulate ethanol consumption via \u03b2\u2010catenin binding to the transcription factors TCF3 and LEF1. The data presented here further implicate GSK3\u03b2 in alcohol consumption and support the use of tideglusib as a potential therapeutic in the treatment of AUD.<\/jats:p>","DOI":"10.1111\/adb.70044","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:17:51Z","timestamp":1747721871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Selective GSK3\u03b2 Inhibitor, Tideglusib, Decreases Intermittent Access and Binge Ethanol Self\u2010Administration in C57BL\/6J Mice"],"prefix":"10.1111","volume":"30","author":[{"given":"Sam","family":"Gottlieb","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Program in Neuroscience Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"van der Vaart","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalise","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Bledsoe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennen","family":"O'Rourke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walker\u00a0D.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Department of Human and Molecular Genetics Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3812-9312","authenticated-orcid":false,"given":"Jennifer\u00a0T.","family":"Wolstenholme","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1532-584X","authenticated-orcid":false,"given":"Michael\u00a0F.","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"VCU Alcohol Research Center Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"SAMHSA \u201c2022 National Survey on Drug Use and Health \u201d in Quality C. f. 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