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The drug acamprosate (Campral\u00ae \u2013 calcium-bis[N-acetylhomotaurinate]) is one of few pharmacological treatments available for AUD. Recent research suggests that the properties of acamprosate may be attributed to calcium, but the acute and long-term effects by calcium supplementation on ethanol-induced dopamine release and relapse-like drinking is not fully known. We used in vivo microdialysis and the alcohol deprivation model, to further define the interaction of local or systemic calcium and ethanol on accumbal dopamine and taurine levels, and to outline the impact of acute and repeated calcium treatment on dopamine and the alcohol deprivation effect (ADE) in male Wistar rats. The role of calcium was further studied by local administration of an L-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel (LTCC) blocker. The results demonstrate that acute local administration of calcium in na\u00efve rats increased nucleus accumbens extracellular dopamine levels, and prevented ethanol from further increasing dopamine. In addition, the ethanol-induced elevation of taurine was delayed in animals receiving calcium. Following sub-chronic systemic calcium administration, the dopamine-elevating property of calcium was lost. The LTCC inhibitor nicardipine decreased accumbal dopamine levels and prevented both calcium and ethanol from altering dopamine output. Acute systemic calcium administration abolished the ADE in treatment-na\u00efve rats, but not in rats pretreated with sub-chronic calcium. Taken together, the results suggest that acute properties of calcium abolish ethanol-induced effects within the mesolimbic dopamine system, while there is an indication of tolerance development to both the dopaminergic and behavioral ethanol-related effects of calcium, thus mimicking the outcomes previously observed with acamprosate.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-03804-1","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:24:53Z","timestamp":1768083893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effects of sub-chronic calcium treatment on ethanol-induced dopamine elevation and the alcohol deprivation effect in the rat"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1241-7690","authenticated-orcid":false,"given":"Karin","family":"Ademar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6229-7178","authenticated-orcid":false,"given":"Klara","family":"Danielsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"S\u00f6derpalm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-9908","authenticated-orcid":false,"given":"Louise","family":"Adermark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Ericson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"3804_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3390\/biomedicines7040099","volume":"7","author":"J Rehm","year":"2019","unstructured":"Rehm J, Shield KD. 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