{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:46:44Z","timestamp":1777052804787,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Studies suggest that serotonin (5-HT) plays an important role in alcohol use disorder (AUD). While several receptor subtypes modulate the role of 5-HT in AUD, evidence suggests that 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2C<\/jats:sub> receptors may be directly involved in alcohol drinking due to their interaction with the mesolimbic dopaminergic system. The aim of the present study was to investigate the effects of 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2C<\/jats:sub> antagonists, alone or in combination, on the acquisition and expression (i.e., return to alcohol drinking after a period of abstinence\/treatment) of voluntary alcohol drinking in male mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Animals had intermittent access to alcohol (10% v\/v) in a two-bottle choice procedure for 30\u202fdays (acquisition), and were then submitted to alcohol re-exposure sessions after periods of abstinence. Vehicle, the 5-HT<jats:sub>2A<\/jats:sub> receptor antagonist M100907 (M100, 1\u202fmg\/kg) and\/or the 5-HT<jats:sub>2C<\/jats:sub> receptor antagonist SB242084 (SB, 1\u202fmg\/kg) were administered either prior to acquisition (Experiment 1) or during the abstinence period preceding re-exposure sessions (Experiment 2). During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings show that combined treatment with 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2C<\/jats:sub> antagonists, but not treatment with the antagonists separately, reduced alcohol drinking and preference when administered immediately before acquisition (Experiment 1). Combined treatment with 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2C<\/jats:sub> antagonists after the establishment of voluntary alcohol drinking did not alter the expression of drinking behavior (Experiment 2). On the other hand, while post-acquisition treatment with a 5-HT<jats:sub>2A<\/jats:sub> antagonist alone decreased alcohol intake and preference during re-exposure, co-administration of a 5-HT<jats:sub>2C<\/jats:sub> antagonist blocked these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest that 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2C<\/jats:sub> receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2025.1639344","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:26:19Z","timestamp":1756099579000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice"],"prefix":"10.3389","volume":"19","author":[{"given":"Sandy C.","family":"Sim\u00f5es","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia N.","family":"Amorim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmim A.","family":"Serra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila S.","family":"Abreu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Clara E.","family":"Santana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o P. 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