{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:41:59Z","timestamp":1785408119852,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,5]]},"group-title":"Animal Behavior and Cognition","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["P50 AA026117"],"award-info":[{"award-number":["P50 AA026117"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R37 AA17531"],"award-info":[{"award-number":["R37 AA17531"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AA26551"],"award-info":[{"award-number":["R01 AA26551"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31 AA32154"],"award-info":[{"award-number":["F31 AA32154"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 NS115704"],"award-info":[{"award-number":["T32 NS115704"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,5]]},"abstract":"<jats:title>\n                  <jats:bold>Abstract<\/jats:bold>\n                <\/jats:title>\n                <jats:p>Despite decades of research, no new FDA-approved medications for alcohol use disorder (AUD) have emerged in over 25 years. Enhancing the translational relevance of preclinical models by more precisely capturing the behavioral and neurobiological features of AUD offers a promising path toward identifying novel therapeutic targets. Operant self-administration paradigms are essential for modeling voluntary ethanol intake in rodents, yet traditional approaches often confound appetitive (seeking) and consummatory (intake) behaviors. The sipper model addresses this limitation by allowing extended, uninterrupted access to ethanol following operant responding, enabling a clearer dissociation between seeking and consumption. In this review, we synthesize key findings from studies employing the sipper model to investigate the behavioral and neurobiological mechanisms underlying alcohol use. We emphasize how over two decades of research employing the sipper model have demonstrated that ethanol- directed behaviors are dynamic processes, shaped by internal states, environmental cues, and prior experience. Finally, we introduce medparser, a new open-source R package designed to standardize the analysis of high-resolution licking data generated by sipper paradigms. By promoting reproducibility and cross-study comparability, this tool supports rigorous behavioral phenotyping. Together, these methodological and analytical advances enhance the translational potential of preclinical models and may ultimately aid in the discovery of novel therapeutic targets for AUD.<\/jats:p>","DOI":"10.1101\/2025.08.04.668445","type":"posted-content","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T21:10:22Z","timestamp":1754428222000},"source":"Crossref","is-referenced-by-count":1,"title":["A review of operant ethanol self-administration using the sipper model: Methodological advances and a novel standardized analysis tool"],"prefix":"10.64898","author":[{"given":"Olivia","family":"Ortelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025080715050572000_2025.08.04.668445v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s44159-023-00167-y"},{"key":"2025080715050572000_2025.08.04.668445v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2024.173802"},{"key":"2025080715050572000_2025.08.04.668445v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-024-06646-1"},{"key":"2025080715050572000_2025.08.04.668445v1.4","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association . (2013). Diagnostic and statistical manual of mental disorders: DSM-5. (5th edition). American Psychiatric Association.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"2025080715050572000_2025.08.04.668445v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2016.12.002"},{"key":"2025080715050572000_2025.08.04.668445v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14924"},{"key":"2025080715050572000_2025.08.04.668445v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15944"},{"key":"2025080715050572000_2025.08.04.668445v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.11.002"},{"key":"2025080715050572000_2025.08.04.668445v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12523"},{"key":"2025080715050572000_2025.08.04.668445v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.10.030"},{"key":"2025080715050572000_2025.08.04.668445v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100877"},{"key":"2025080715050572000_2025.08.04.668445v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3238-y"},{"key":"2025080715050572000_2025.08.04.668445v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2008.01.005"},{"key":"2025080715050572000_2025.08.04.668445v1.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00797.x"},{"key":"2025080715050572000_2025.08.04.668445v1.15","doi-asserted-by":"publisher","DOI":"10.2307\/1536346"},{"key":"2025080715050572000_2025.08.04.668445v1.16","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000171944.50381.86"},{"key":"2025080715050572000_2025.08.04.668445v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1465-z"},{"key":"2025080715050572000_2025.08.04.668445v1.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2012.01774.x"},{"key":"2025080715050572000_2025.08.04.668445v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13562"},{"key":"2025080715050572000_2025.08.04.668445v1.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02220.x"},{"key":"2025080715050572000_2025.08.04.668445v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(02)00963-0"},{"key":"2025080715050572000_2025.08.04.668445v1.22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00094.x"},{"key":"2025080715050572000_2025.08.04.668445v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2006.09.033"},{"key":"2025080715050572000_2025.08.04.668445v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1999.tb04047.x"},{"key":"2025080715050572000_2025.08.04.668445v1.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02467.x"},{"key":"2025080715050572000_2025.08.04.668445v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(02)00236-7"},{"key":"2025080715050572000_2025.08.04.668445v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16533"},{"key":"2025080715050572000_2025.08.04.668445v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2020.07.024"},{"key":"2025080715050572000_2025.08.04.668445v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.01.030"},{"key":"2025080715050572000_2025.08.04.668445v1.30","doi-asserted-by":"publisher","DOI":"10.1037\/10627-000"},{"key":"2025080715050572000_2025.08.04.668445v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2009.05.012"},{"key":"2025080715050572000_2025.08.04.668445v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.02.028"},{"key":"2025080715050572000_2025.08.04.668445v1.33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02209.x"},{"key":"2025080715050572000_2025.08.04.668445v1.34","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0292-19.2019"},{"key":"2025080715050572000_2025.08.04.668445v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2024.105544"},{"key":"2025080715050572000_2025.08.04.668445v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.11.008"},{"key":"2025080715050572000_2025.08.04.668445v1.37","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3571-9"},{"issue":"2","key":"2025080715050572000_2025.08.04.668445v1.38","first-page":"141","article-title":"Chronobiological Regulation of Alcohol Intake","volume":"25","year":"2001","journal-title":"Alcohol Research & Health"},{"key":"2025080715050572000_2025.08.04.668445v1.39","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12631"},{"key":"2025080715050572000_2025.08.04.668445v1.40","doi-asserted-by":"publisher","DOI":"10.1037\/pha0000756"},{"key":"2025080715050572000_2025.08.04.668445v1.41","unstructured":"Kassambara, A. , & Mundt, F. (2020). factoextra: Extract and Visualize the Results of Multivariate Data Analyses (Version 1.0.7) [Computer software]. https:\/\/cran.r-project.org\/web\/packages\/factoextra\/index.html"},{"key":"2025080715050572000_2025.08.04.668445v1.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002055"},{"key":"2025080715050572000_2025.08.04.668445v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.08.007"},{"key":"2025080715050572000_2025.08.04.668445v1.44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00830.x"},{"key":"2025080715050572000_2025.08.04.668445v1.45","doi-asserted-by":"crossref","unstructured":"McCool, B. A. , Christian, D. , Fetzer, J. , & Chappell, A . (2014). Lateral\/basolateral amygdala serotonin type-2 receptors modulate operant self-administration of a sweetened ethanol solution via inhibition of principal neuron activity. Frontiers in Integrative Neuroscience, 8. https:\/\/www.frontiersin.org\/articles\/10.3389\/fnint.2014.00005","DOI":"10.3389\/fnint.2014.00005"},{"key":"2025080715050572000_2025.08.04.668445v1.46","unstructured":"National Survey on Drug Use and Health. (2023). 2021 NSDUH Annual National Report. Substance Abuse and Mental Health Services Administration. https:\/\/www.samhsa.gov\/data\/report\/2021-nsduh-annual-national-report"},{"key":"2025080715050572000_2025.08.04.668445v1.47","doi-asserted-by":"publisher","DOI":"10.32614\/CRAN.package.medparser"},{"key":"2025080715050572000_2025.08.04.668445v1.48","doi-asserted-by":"publisher","DOI":"10.1111\/acer.15293"},{"key":"2025080715050572000_2025.08.04.668445v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.addicn.2025.100196"},{"key":"2025080715050572000_2025.08.04.668445v1.50","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0506-22.2023"},{"key":"2025080715050572000_2025.08.04.668445v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(01)00157-4"},{"key":"2025080715050572000_2025.08.04.668445v1.52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02267.x"},{"key":"2025080715050572000_2025.08.04.668445v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(01)00200-2"},{"key":"2025080715050572000_2025.08.04.668445v1.54","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.2002.63.107"},{"key":"2025080715050572000_2025.08.04.668445v1.55","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000121649.81642.3F"},{"key":"2025080715050572000_2025.08.04.668445v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2004.02.002"},{"key":"2025080715050572000_2025.08.04.668445v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(03)54004-1"},{"key":"2025080715050572000_2025.08.04.668445v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2003.09.002"},{"key":"2025080715050572000_2025.08.04.668445v1.59","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2000.tb02054.x"},{"key":"2025080715050572000_2025.08.04.668445v1.60","doi-asserted-by":"publisher","DOI":"10.1007\/s002130051167"},{"key":"2025080715050572000_2025.08.04.668445v1.61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1998.tb03980.x"},{"key":"2025080715050572000_2025.08.04.668445v1.62","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjaa056"},{"key":"2025080715050572000_2025.08.04.668445v1.63","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02309.x"},{"key":"2025080715050572000_2025.08.04.668445v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(02)00318-X"},{"key":"2025080715050572000_2025.08.04.668445v1.65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00753.x"},{"key":"2025080715050572000_2025.08.04.668445v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2018.10"},{"key":"2025080715050572000_2025.08.04.668445v1.67","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000160084.13148.02"},{"key":"2025080715050572000_2025.08.04.668445v1.68","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3896-z"},{"key":"2025080715050572000_2025.08.04.668445v1.69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01653.x"},{"key":"2025080715050572000_2025.08.04.668445v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agaf011"},{"key":"2025080715050572000_2025.08.04.668445v1.71","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.4308"},{"key":"2025080715050572000_2025.08.04.668445v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.07.011"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.04.668445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:17:05Z","timestamp":1768468625000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.04.668445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":72,"URL":"https:\/\/doi.org\/10.1101\/2025.08.04.668445","relation":{},"subject":[],"published":{"date-parts":[[2025,8,5]]},"subtype":"preprint"}}