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The current experiments investigate the neural mechanisms underlying binge\u2010like ethanol drinking, focusing on the involvement of Y1R+ CeA\u2010to\u2010lateral hypothalamus (LH) projections, dynamic interactions between Y1R and Y2R within the CeA, and the impact of chronic ethanol exposure on Y1R protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NPY1R\u2010ires\u2010cre mice received LH cannulation, were infused with cre\u2010dependent inhibitory (Gi) Designer Receptor Exclusively Activated by Designer Drug (DREADD) or control virus into the CeA, and went through drinking in the dark (DID). Other animals were treated intra\u2010CeA with an NPY overexpression vector (FIB\u2010NPY) or control, and went through DID, intermittent access to ethanol (IAE), and open\u2010field testing. Viral placements and receptor targets were assessed via qPCR. Finally, mice went through six cycles of DID, and Y1R immunohistochemical (IHC) labeling on neurons was assessed for animals sacrificed after the final DID session or after a 24\u2010h period of abstinence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chemogenetic inhibition of Y1R+ CeA\u2010LH projections selectively reduced binge\u2010like ethanol drinking in male mice without affecting female mice. Viral NPY overexpression revealed behavioral effects and predictive relationships between receptor mRNA expression and intake patterns. Although no significant differences were found in Y1R\/NeuN colocalization across sex and treatment groups, correlational analyses revealed that Y1R expression varied with individual ethanol consumption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, these results support a model wherein Y1R signaling within the CeA regulates ethanol consumption through circuit\u2010specific mechanisms and broader neuroadaptive changes influenced by sex and individual drinking patterns. This research advances our understanding of the neurobiological mechanisms underlying binge\u2010like ethanol intake and highlights the complex, sex\u2010dependent roles of NPY\u2010Y1R and Y2R signaling in the CeA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70151","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T06:05:19Z","timestamp":1756533919000},"page":"2146-2162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuropeptide <scp>Y1<\/scp> receptor expressing circuit from the central amygdala to lateral hypothalamus modulates binge\u2010like ethanol consumption in a sex\u2010dependent manner"],"prefix":"10.1111","volume":"49","author":[{"given":"Sophie C.","family":"Bendrath","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlyn","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-504X","authenticated-orcid":false,"given":"Anne M.","family":"Dankert","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-9256","authenticated-orcid":false,"given":"Todd E.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Bowles Center for Alcohol Studies University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2022.03.025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02225.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14963"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.01.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011163"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsgos.2024.100405"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000075827.74538.FE"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201000100"},{"key":"e_1_2_8_10_1","first-page":"1564","article-title":"Differential expression of NPY and its receptors in alcohol\u2010preferring AA and alcohol\u2010avoiding ANA rats","volume":"25","author":"Caberlotto L.","year":"2001","journal-title":"Alcoholism, Clinical and Experimental Research"},{"key":"e_1_2_8_11_1","first-page":"1274","article-title":"Vital signs: binge drinking among high school students and adults \u2010\u2010\u2010 United States, 2009","volume":"59","author":"Centers for Disease Control and Prevention (CDC)","year":"2010","journal-title":"MMWR. 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