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Despite this, FDA approved treatments for AUD are limited. For this reason, further understanding of the neurobiological mechanisms in AUD is required for new treatments. An aspect of AUD involves deficits in behavioral flexibility that is similarly seen in animal models with depletion of dorsal striatal cholinergic interneurons (CINs). We found that acute EtOH (40 mM) inhibits the firing rate of dorsal striatal CINs, which are the primary source of acetylcholine (ACh) in the dorsal striatum. Additionally, we found through slice photometry recordings using an intensity-based ACh sensing fluorescent reporter (iAChSnFR) that acute EtOH (40 mM) inhibits dorsal striatal ACh release. In accord, in vivo fiber photometry with iAChSnFR also showed inhibition of ACh release following acute EtOH (2 g\/kg ip). To induce EtOH dependence in mice, we used the chronic intermittent EtOH (CIE) vapor exposure model. Following CIE, we found that CIE-treated mice had a significant depression of ACh release compared to control mice in the dorsomedial but not dorsolateral striatum. Then, we performed stereological cell counts of CINs in CIE and control mice to examine the cause of this ACh deficit and found that CIE mice had a significant decrease in CINs in the dorsomedial but not dorsolateral striatum. In conclusion, our data show that EtOH inhibits dorsal striatal cholinergic signaling in a subregion specific manner that may contribute to AUD related behaviors.<\/jats:p>","DOI":"10.1101\/2025.05.30.656893","type":"posted-content","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:30:23Z","timestamp":1749015023000},"source":"Crossref","is-referenced-by-count":0,"title":["Ethanol inhibits dorsomedial striatum acetylcholine release"],"prefix":"10.64898","author":[{"given":"Logan E.","family":"Slade","sequence":"first","affiliation":[{"name":"Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C.","family":"Levy","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Mitcham","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando G.","family":"Salinas","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041200553592000_2025.05.30.656893v1.1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. 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