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We previously showed that vulnerability to compulsive-like alcohol use can be modeled in rats using punished alcohol self-administration and in male rats is mediated by PKC\u03b4+ neurons in the central nucleus of the amygdala (CeA). Here, we used cell-type-specific transcriptomics to identify molecular mechanisms underlying individual differences in this behavior. Transcriptional changes were restricted to a limited number of CeA neuronal populations, including PKC\u03b4+ neurons, where weighted Gene Co-expression Network Analysis identified an upregulated co-expression module in punishment-resistant rats with FGFR1 as a druggable upstream regulator. Selective silencing of\n                    <jats:italic>FgfR1<\/jats:italic>\n                    in PKC\u03b4+ neurons normalized elevated PKC\u03b4+ expression, and reduced punishment-resistant alcohol self-administration. This effect was recapitulated by systemic administration of the FgfR1-antagonist PD173074. These findings identify distinct CeA circuits that promote addiction vulnerability, and position FGFR1 as potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-77302-9","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:23:28Z","timestamp":1788369808000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and validation of central amygdala FGFR1 as a therapeutic target for alcohol use disorder using single-nucleus sequencing in rats"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-1855","authenticated-orcid":false,"given":"Estelle","family":"Barbier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"H\u00f6glund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6307-9906","authenticated-orcid":false,"given":"Li","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9973-6437","authenticated-orcid":false,"given":"Nihal A.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9012-137X","authenticated-orcid":false,"given":"Elizabeth A.","family":"Osterndorff-Kahanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-2628","authenticated-orcid":false,"given":"Riccardo","family":"Barchiesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3085-8365","authenticated-orcid":false,"given":"Antonio","family":"Lacorte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5237-6179","authenticated-orcid":false,"given":"Lief E.","family":"Fenno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-4431","authenticated-orcid":false,"given":"Robert O.","family":"Messing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8045-1789","authenticated-orcid":false,"given":"R. 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The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"9407"}}