{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:54:04Z","timestamp":1787032444717,"version":"build-2736575974"},"posted":{"date-parts":[[2026,4,5]]},"group-title":"Neuroscience","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["5P60AA011605-29"],"award-info":[{"award-number":["5P60AA011605-29"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["U01AA02091"],"award-info":[{"award-number":["U01AA02091"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIDA","award":["K01DA061050"],"award-info":[{"award-number":["K01DA061050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Neuroimmune signaling is increased in postmortem brain tissue from individuals with alcohol use disorder (AUD), and growing evidence suggests that it contributes to persistent alcohol-related neuroadaptations. Interferon regulatory factor 7 (IRF7), a transcription factor downstream of endosomal Toll-like receptor signaling, is induced in alcohol-relevant brain regions and may contribute to escalated drinking. Here, we tested whether chronic intermittent ethanol (CIE) vapor exposure engages IRF7 signaling during subsequent alcohol self-administration and whether this is associated with altered molecular E\/I balance in the aIC and altered functional E\/I balance in aIC\u2794nucleus accumbens projection neurons. Female Wistar rats (n=30) were trained to self-administer alcohol (15% v\/v; FR2 vs inactive lever) during 30-minute sessions. After establishing baseline drinking, rats underwent 1-3 cycles of CIE, which increased alcohol self-administration at the 72 h post vapor test. This increase positively correlated with IRF7 levels in the anterior insular cortex (aIC) and nucleus accumbens, while molecular, and immunofluorescence showed that CIE shifted aIC excitatory\/inhibitory (E\/I) balance toward reduced excitation. Electrophysiological recordings further showed reduced functional E\/I balance in aIC neurons projecting to the nucleus accumbens. Knockdown of IRF7 in the aIC attenuated CIE induced escalation of alcohol self-administration, supporting a role for insular IRF7 signaling in alcohol related neuroadaptations that promote escalated drinking.<\/jats:p>","DOI":"10.64898\/2026.04.01.715945","type":"posted-content","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:30:14Z","timestamp":1775449814000},"source":"Crossref","is-referenced-by-count":1,"title":["Interferon-Regulatory Factor 7: A Neuroimmune Role for Vapor-Induced Escalations in Ethanol Self-Administration"],"prefix":"10.64898","author":[{"given":"Dennis F","family":"Lovelock","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M","family":"Carew","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M","family":"McNair","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baylee M","family":"Materia","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi Z","family":"Darawsheh","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M","family":"Downs","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"},{"name":"Department of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Sizer","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"},{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A","family":"McDonald","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe A","family":"McElligott","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"},{"name":"Department of Pharmacology"},{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Leon G","family":"Coleman","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"},{"name":"Department of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-8376","authenticated-orcid":false,"given":"Joyce","family":"Besheer","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies"},{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040901350930000_2026.04.01.715945v2.1","doi-asserted-by":"crossref","first-page":"e70486","DOI":"10.1002\/alz.70486","article-title":"Loss of lysosomal acid lipase contributes to Alzheimer\u2019s disease pathology and cognitive decline","volume":"21","year":"2025","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026040901350930000_2026.04.01.715945v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4415"},{"key":"2026040901350930000_2026.04.01.715945v2.3","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12932"},{"key":"2026040901350930000_2026.04.01.715945v2.4","doi-asserted-by":"crossref","first-page":"138012","DOI":"10.1016\/j.neulet.2024.138012","article-title":"Alcohol exposure induces cortical activity change during quiescent state","volume":"843","year":"2024","journal-title":"Neuroscience Letters"},{"key":"2026040901350930000_2026.04.01.715945v2.5","doi-asserted-by":"crossref","unstructured":"Coleman Jr LG , Crews FT (2018) Innate immune signaling and alcohol use disorders. 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