{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:10:05Z","timestamp":1792786205699,"version":"4.5.0"},"posted":{"date-parts":[[2025,6,8]]},"group-title":"Neuroscience","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["F32AA031396"],"award-info":[{"award-number":["F32AA031396"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50AA017823"],"award-info":[{"award-number":["P50AA017823"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA029403"],"award-info":[{"award-number":["R01AA029403"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA031472"],"award-info":[{"award-number":["R01AA031472"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["R01NS07816"],"award-info":[{"award-number":["R01NS07816"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["T32NS115667"],"award-info":[{"award-number":["T32NS115667"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["AHA 24PRE1201066"],"award-info":[{"award-number":["AHA 24PRE1201066"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Republic of T\u00fcrkiye Ministry of National Education Scholarship","id":[{"id":"https:\/\/ror.org\/00jga9g46","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04p491231","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Sciences","award":["T32GM154124"],"award-info":[{"award-number":["T32GM154124"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The cortex is one of the last brain regions to fully mature, making it particularly sensitive to early life drug use. Both human and rodent studies find long-lasting behavioral changes after adolescent alcohol exposure that implicate underlying disruptions in cortical development, including structural abnormalities and altered functional connectivity. Few rodent studies have been conducted across biological scales (from single cell, whole brain network, to behavior) to understand the comprehensive implications of these disruptions. We assessed how adolescent binge-like alcohol consumption in a drinking in the dark (DID) model affected adult alcohol consumption, behavioral exploration, brain-wide functional connectivity, and intrinsic cellular excitability in mice. Only female mice exposed to alcohol during adolescence exhibited aversion-resistant alcohol preference, as well as increased exploration in the elevated plus maze. Resting state neuroimaging revealed broad sex-specific changes in brain-wide networks. Finally, we identify\n                  <jats:italic>ex vivo<\/jats:italic>\n                  intrinsic excitability alterations in key brain regions known to be susceptible to adolescent perturbations identified in neural networks, with greater effects in males, allowing biological and mechanistic targets to be further explored for future study and interventions. Our results show that females may be more vulnerable to lasting addiction-related behavioral and brain connectivity consequences of adolescent alcohol exposure, corroborating human and rodent studies demonstrating that adolescent alcohol use may increase risk for adult alcohol use more strongly in females. We further show that while males do not show identical behavioral changes, they critically show alterations in intrinsic excitability and cellular function, suggesting divergent sex-specific adaptations to adolescent binge drinking.\n                <\/jats:p>","DOI":"10.1101\/2025.06.05.658112","type":"posted-content","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T03:00:48Z","timestamp":1749438048000},"source":"Crossref","is-referenced-by-count":0,"title":["Adolescent alcohol consumption differentially alters sexually-divergent behaviors and infralimbic cortex function in mice"],"prefix":"10.64898","author":[{"given":"Laurel R.","family":"Seemiller","sequence":"first","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayreddin Said","family":"\u00dcnsal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Electrical and Electronics Engineering, Abdullah G\u00fcl University, Kayseri, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Shakhawat","family":"Hossain","sequence":"additional","affiliation":[{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery R.","family":"Sicher","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleah","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Johnson-Dendy","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily P.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren N.","family":"Beloate","sequence":"additional","affiliation":[{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-7378","authenticated-orcid":false,"given":"Patrick J.","family":"Drew","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanyin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-7929","authenticated-orcid":false,"given":"Nicole A.","family":"Crowley","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Penn State Neuroscience Institute, The Huck Institutes of the Life Sciences, University Park, PA, 16802, USA"},{"name":"Center for Neural Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA"},{"name":"Department Neurosurgery, The Pennsylvania State University, University Park, PA, 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026101119101443000_2025.06.05.658112v3.1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1176\/appi.ajp.157.5.745","article-title":"Age at First Alcohol Use: A Risk Factor for the Development of Alcohol Disorders","volume":"157","year":"2000","journal-title":"AJP"},{"key":"2026101119101443000_2025.06.05.658112v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-3289(97)90009-2"},{"key":"2026101119101443000_2025.06.05.658112v3.3","first-page":"2060","article-title":"Links between adolescent binge drinking and midlife alcohol use behaviors by age, sex, and race\/ethnicity. Alcohol","volume":"48","year":"2024","journal-title":"Clinical and Experimental Research"},{"key":"2026101119101443000_2025.06.05.658112v3.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jadohealth.2012.05.006"},{"key":"2026101119101443000_2025.06.05.658112v3.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01457-4"},{"key":"2026101119101443000_2025.06.05.658112v3.6","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhx014"},{"key":"2026101119101443000_2025.06.05.658112v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.01.044"},{"key":"2026101119101443000_2025.06.05.658112v3.8","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2011.72.1019"},{"key":"2026101119101443000_2025.06.05.658112v3.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-7358(99)00027-6"},{"key":"2026101119101443000_2025.06.05.658112v3.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.11.044"},{"key":"2026101119101443000_2025.06.05.658112v3.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2004.10.007"},{"key":"2026101119101443000_2025.06.05.658112v3.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117094"},{"key":"2026101119101443000_2025.06.05.658112v3.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2013.02.008"},{"key":"2026101119101443000_2025.06.05.658112v3.14","doi-asserted-by":"publisher","DOI":"10.1037\/tps0000198"},{"key":"2026101119101443000_2025.06.05.658112v3.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109561"},{"key":"2026101119101443000_2025.06.05.658112v3.16","doi-asserted-by":"crossref","first-page":"100171","DOI":"10.1016\/j.addicn.2024.100171","article-title":"Voluntary adolescent alcohol exposure does not robustly increase adulthood consumption of alcohol in multiple mouse and rat models","volume":"12","year":"2024","journal-title":"Addiction Neuroscience"},{"key":"2026101119101443000_2025.06.05.658112v3.17","doi-asserted-by":"crossref","unstructured":"Dao NC , Suresh Nair M , Magee SN , Moyer JB , Sendao V , Brockway DF , et al. Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions. Frontiers in Behavioral Neuroscience. 2020;14.","DOI":"10.3389\/fnbeh.2020.00086"},{"key":"2026101119101443000_2025.06.05.658112v3.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026101119101443000_2025.06.05.658112v3.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.10.018"},{"key":"2026101119101443000_2025.06.05.658112v3.20","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"2026101119101443000_2025.06.05.658112v3.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112976"},{"key":"2026101119101443000_2025.06.05.658112v3.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01050-1"},{"key":"2026101119101443000_2025.06.05.658112v3.23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0684-15.2015"},{"key":"2026101119101443000_2025.06.05.658112v3.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-025-06985-7"},{"key":"2026101119101443000_2025.06.05.658112v3.25","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12821"},{"key":"2026101119101443000_2025.06.05.658112v3.26","doi-asserted-by":"crossref","first-page":"e1194","DOI":"10.1038\/tp.2017.161","article-title":"Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction","volume":"7","year":"2017","journal-title":"Transl Psychiatry"},{"key":"2026101119101443000_2025.06.05.658112v3.27","doi-asserted-by":"crossref","first-page":"112999","DOI":"10.1016\/j.drugalcdep.2025.112999","article-title":"Alcohol-seeking associations with resting state functional connectivity of the amygdala","volume":"278","year":"2026","journal-title":"Drug and Alcohol Dependence"},{"key":"2026101119101443000_2025.06.05.658112v3.28","unstructured":"Association AP . Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association; 2013."},{"key":"2026101119101443000_2025.06.05.658112v3.29","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-023-00565-0"},{"key":"2026101119101443000_2025.06.05.658112v3.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.08.001"},{"key":"2026101119101443000_2025.06.05.658112v3.31","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1001\/jamapsychiatry.2017.2161","article-title":"Prevalence of 12-Month Alcohol Use, High-Risk Drinking, and DSM-IV Alcohol Use Disorder in the United States, 2001-2002 to 2012-2013: Results From the National Epidemiologic Survey on Alcohol and Related Conditions","volume":"74","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2026101119101443000_2025.06.05.658112v3.32","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhx014"},{"key":"2026101119101443000_2025.06.05.658112v3.33","doi-asserted-by":"crossref","first-page":"101294","DOI":"10.1016\/j.dcn.2023.101294","article-title":"Associations between alcohol use and sex-specific maturation of subcortical gray matter morphometry from adolescence to adulthood: Replication across two longitudinal samples","volume":"63","year":"2023","journal-title":"Developmental Cognitive Neuroscience"},{"key":"2026101119101443000_2025.06.05.658112v3.34","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2500-4"},{"key":"2026101119101443000_2025.06.05.658112v3.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2007.09.012"},{"key":"2026101119101443000_2025.06.05.658112v3.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2012.07.012"},{"key":"2026101119101443000_2025.06.05.658112v3.37","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-A A , Dannenhoffer CA , Elton A , Lee S-H , Ban W , Shih Y-YI , et al. Altered Cortico-Subcortical Network After Adolescent Alcohol Exposure Mediates Behavioral Deficits in Flexible Decision-Making. Front Pharmacol. 2021;12.","DOI":"10.3389\/fphar.2021.778884"},{"key":"2026101119101443000_2025.06.05.658112v3.38","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13004"},{"key":"2026101119101443000_2025.06.05.658112v3.39","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12914"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.05.658112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:10:30Z","timestamp":1791771030000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.05.658112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,8]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1101\/2025.06.05.658112","relation":{},"subject":[],"published":{"date-parts":[[2025,6,8]]},"subtype":"preprint"}}