{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:57:05Z","timestamp":1785412625119,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,16]]},"group-title":"Neuroscience","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AA022048"],"award-info":[{"award-number":["R01AA022048"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32AA007573"],"award-info":[{"award-number":["T32AA007573"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Binge alcohol drinking increases the risk of developing an alcohol use disorder (AUD) and comorbid psychopathology. The lateral hypothalamus (LH) is a brain structure that integrates cognitive and sensory information to tightly regulate motivated behavior, including binge drinking. Importantly, LH function is vulnerable to modulation by the pro-stress neuropeptide corticotropin-releasing factor (CRF), and acute antagonism of CRF receptor 1 (CRFR1) in the LH blunts binge drinking. However, the role of LH CRFR1 in chronic binge drinking is unknown. We used genetically targeted knockdown (KD) of CRFR1 in the LH of male and female mice followed by three weeks of binge drinking using the \u201cDrinking in the Dark\u201d (DID) model. CRFR1 KD in the posterior LH increased alcohol consumption, independent of sex, with no effect of KD in the anterior LH. Consistent with this, total alcohol consumption was negatively correlated with the location of CRFR1 KD in the LH along the anterior-posterior axis. CRFR1 KD did not alter water consumption or body weight, suggesting the effects of CRFR1 KD on alcohol consumption were not due to broad disruption of fluid intake or homeostatic function. In contrast to the observed effects on binge drinking, CRFR1 KD increased anxiety-like behavior and blunted sucrose preference, independent of KD location in the LH. Our findings provide foundational insight into LH function in the context of AUD and prompt further investigation into the divergent roles that distinct circuitry or cell populations along the anterior-posterior axis of the LH may play in binge drinking.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>CRFR1 knockdown in posterior LH increased alcohol drinking independent of sex<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Alcohol intake negatively correlated with AP location of CRFR1 knockdown in LH<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>CRFR1 knockdown was anxiogenic with more pronounced effects in females<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Sucrose preference was blunted by CRFR1 knockdown<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.16.676507","type":"posted-content","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:05:16Z","timestamp":1758049516000},"source":"Crossref","is-referenced-by-count":0,"title":["Lateral hypothalamus CRFR1 regulation of chronic binge drinking: divergence along anterior-posterior axis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5270-8877","authenticated-orcid":false,"given":"Jobe","family":"Ritchie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-5872","authenticated-orcid":false,"given":"Maya","family":"Eberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-5482","authenticated-orcid":false,"given":"Jessica","family":"Wojick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Campeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3790-3902","authenticated-orcid":false,"given":"Lili","family":"Kooyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-9256","authenticated-orcid":false,"given":"Todd","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-4495","authenticated-orcid":false,"given":"Thomas","family":"Kash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091820200921000_2025.09.16.676507v1.1","unstructured":"SAMHSA. 2023 National Survey on Drug Use and Health. Table 2.9B\u2014Alcohol, binge alcohol, and heavy alcohol use in past month: among people aged 12 or older; by detailed age category, percentages, 2022 and 2023. Center for Behavioral Health Statistics and Quality."},{"key":"2025091820200921000_2025.09.16.676507v1.2","unstructured":"NIDAAA. What Colleges Need to Know Now - An Update on College Drinking Research. (2007)."},{"key":"2025091820200921000_2025.09.16.676507v1.3","unstructured":"CDC. Alcohol and Public Health: Alcohol-Related Disease Impact (ARDI). Centers for Disease Control and prevention."},{"key":"2025091820200921000_2025.09.16.676507v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2011.06.045"},{"key":"2025091820200921000_2025.09.16.676507v1.5","doi-asserted-by":"publisher","DOI":"10.1081\/ADA-200032331"},{"key":"2025091820200921000_2025.09.16.676507v1.6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/164_2017_86","volume-title":"The Neuropharmacology of Alcohol","volume":"248","year":"2018"},{"key":"2025091820200921000_2025.09.16.676507v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6256-11.2012"},{"key":"2025091820200921000_2025.09.16.676507v1.8","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1530-0277.2011.01610.x","article-title":"Corticotropin-Releasing Factor Acting on Corticotropin-Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice","volume":"36","year":"2012","journal-title":"Alcoholism Clin &amp; Exp Res"},{"key":"2025091820200921000_2025.09.16.676507v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.209"},{"key":"2025091820200921000_2025.09.16.676507v1.10","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/j.1530-0277.2007.00379.x","article-title":"Increased Drinking During Withdrawal From Intermittent Ethanol Exposure Is Blocked by the CRF Receptor AntagonistD-Phe-CRF(12\u201341)","volume":"31","year":"2007","journal-title":"Alcoholism Clin &amp; Exp Res"},{"key":"2025091820200921000_2025.09.16.676507v1.11","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-77-18766"},{"key":"2025091820200921000_2025.09.16.676507v1.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.135.3501.375"},{"key":"2025091820200921000_2025.09.16.676507v1.13","doi-asserted-by":"crossref","unstructured":"Pomrenze, M. 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