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We evaluated whether 3,4-methylenedioxymethamphetamine (MDMA), given in a therapy-adjunctive fashion (30\u2009min before fear extinction), could facilitate extinction of conditioned fear and reduce alcohol consumption in a rat model that combines fear conditioning, binge-like alcohol access, abstinence, and re-exposure. Inbred alcohol-preferring (iP) and outbred Wistar rats of both sexes underwent auditory fear conditioning, voluntary ethanol drinking, and subsequently fear extinction after MDMA or vehicle administration, with drug-free extinction recall and alcohol consumption assessed thereafter. Fear conditioning increased voluntary alcohol intake only in iP rats, suggesting a genotype-related fear\u2013alcohol contingency. MDMA acutely reduced freezing during extinction, but ultimately reshaped across-session freezing patterns in a strain- and sex-dependent manner. There were no lasting MDMA treatment effects on next-day drug-free recall. MDMA also altered on-drug fear-expression during extinction without affecting later recall in an iP rat cohort without prior alcohol exposure, indicating the effect is not secondary to drinking history. Critically, MDMA prevented the shock-related increase in alcohol consumption but only in iP rats. These data suggest MDMA\u2019s most reliable action in this model is to disrupt trauma-linked escalation of alcohol intake in genetically- and experientially- vulnerable rats, rather than to globally enhance fear extinction.<\/jats:p>","DOI":"10.1038\/s41386-026-02394-2","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:58:46Z","timestamp":1774627126000},"page":"1556-1567","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MDMA alters fear extinction, and reduces alcohol consumption in inbred alcohol preferring iP rats but not outbred Wistar rats"],"prefix":"10.1038","volume":"51","author":[{"given":"Kade L.","family":"Huckstep","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billi","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annai","family":"Charlton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Pearl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier J.","family":"Maddern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-3634","authenticated-orcid":false,"given":"Robyn M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9061-6463","authenticated-orcid":false,"given":"Gavan P.","family":"McNally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan I.","family":"Lubman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Arunogiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten C.","family":"Morley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-6897","authenticated-orcid":false,"given":"Erin J.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-727X","authenticated-orcid":false,"given":"Andrew J.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-2743","authenticated-orcid":false,"given":"Leigh C.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2394_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/gbb.12349","volume":"16","author":"NW Gilpin","year":"2017","unstructured":"Gilpin NW, Weiner JL. 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