{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:16:41Z","timestamp":1792120601831,"version":"4.4.0"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1FI2GM154674\u201001"],"award-info":[{"award-number":["1FI2GM154674\u201001"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. Ethanol is mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde and further to acetate via aldehyde dehydrogenases (ALDHs). Understanding how ethanol and its metabolites work together to initiate and drive continued ethanol consumption is crucial for identifying interventions for alcohol use disorder (AUD). Therefore, the goal of our study was to determine how ADH1, which is mainly peripherally expressed and metabolizes &gt;90% of ingested ethanol, modulates ethanol metabolite distribution and downstream behaviors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ethanol consumption in drinking\u2010in\u2010the\u2010dark (DID) and two\u2010bottle choice (2BC) drinking paradigms, ethanol metabolite concentrations, and lickometry were assessed after ADH1 inhibition and\/or in\n                      <jats:italic>Adh1<\/jats:italic>\n                      \u2010knockout (\n                      <jats:italic>Adh1<\/jats:italic>\n                      KO) mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:italic>Adh1<\/jats:italic>\n                      KO mice of both sexes exhibited decreased ethanol consumption and preference compared with wild\u2010type (WT) mice in DID and 2BC. ADH1 inhibitor fomepizole (4\u2010MP) also significantly decreased normal and sweetened ethanol consumption in DID studies. Measurement of ethanol and its metabolites revealed that ethanol was increased at 1\u2009h but not 15\u2009min, peripheral acetaldehyde was slightly decreased at both timepoints, and ethanol\u2010induced increases in acetate were abolished after ethanol administration in\n                      <jats:italic>Adh1<\/jats:italic>\n                      KO mice compared with controls. Similarly, ethanol accumulation as a function of consumption was 2\u2010fold higher in\n                      <jats:italic>Adh1<\/jats:italic>\n                      KO or 4\u2010MP\u2010treated mice compared with controls. We then used lickometry to determine how this perturbation in ethanol metabolism affects drinking microstructure.\n                      <jats:italic>Adh1<\/jats:italic>\n                      KO mice consume most of their ethanol in the first 30\u2009min, like WT mice, but display altered temporal shifts in drinking behaviors and do not form normal bout structures, resulting in lower ethanol consumption.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrates that ADH1\u2010mediated ethanol metabolism is a key determinant of ethanol consumption, highlighting a fundamental knowledge gap regarding how ethanol and its metabolites drive ethanol consumption.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70036","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T06:01:41Z","timestamp":1742709701000},"page":"970-984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9840-2013","authenticated-orcid":false,"given":"Bryan","family":"Mackowiak","sequence":"first","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-2557","authenticated-orcid":false,"given":"David L.","family":"Haggerty","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Lehner","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3458-799X","authenticated-orcid":false,"given":"Yu\u2010Hong","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojie","family":"Fu","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Pawlosky","sequence":"additional","affiliation":[{"name":"Office of the Scientific Director, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Ren","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhyo","family":"Seo","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Lovinger","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.10.032"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2020.01.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14924"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01031.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-010-9414-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12436"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-01994-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-05262-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2012.08.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.2c00784"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00005.2014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01752-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02255966"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.16796"},{"key":"e_1_2_9_16_1","first-page":"5","article-title":"The genetics of alcohol metabolism","volume":"30","author":"Edenberg H.J.","year":"2007","journal-title":"Alcohol Research and Health"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4611"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010024\u201001063\u20102"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03502.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3727\/105221617X695519"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1983.tb05498.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01027.x"},{"issue":"35","key":"e_1_2_9_24_1","article-title":"A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence","volume":"1","author":"Guerrini I.","year":"2006","journal-title":"Substance Abuse Treatment, Prevention, and Policy"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908137116"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881116684338"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.77411"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.07.019"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1997.tb03370.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12709"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2013.00080"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1788-6"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65153"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00357-z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01439.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2011.02190.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.legalmed.2009.02.043"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.07.031"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12030524"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4AY00699B"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.1244"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agad077"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.040"},{"key":"e_1_2_9_44_1","doi-asserted-by":"crossref","unstructured":"Luczak S.E. Glatt S.J.&Wall T.L.(2009)Meta\u2010analyses of ALDH2 and ADH1B with alcohol dependence in Asians American Psychological Association Washington DC US.","DOI":"10.1037\/11855-026"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1976.tb03201.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14954"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650701373796"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1700-7"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14416"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.08.020"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2013.00081"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01099.x"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2013.00086"},{"key":"e_1_2_9_54_1","first-page":"23","article-title":"Acetaldehyde\u2010reinforcing effects: a study on oral self\u2010administration behavior","volume":"1","author":"Peana A.","year":"2010","journal-title":"Frontiers in Psychiatry"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00574.x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.04.001"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18309"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0506-22.2023"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb17715.x"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109643"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.12.001"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02543.x"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12734"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90359-8"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2010.09.020"},{"key":"e_1_2_9_66_1","first-page":"39A","article-title":"First\u2010in\u2010human clinical trial of DCR\u2010AUD: evaluation of siRNA knockdown of hepatic acetaldehyde dehydrogenase 2 using a novel bioanalytic assay","volume":"46","author":"Zhang X.Y.F.","year":"2022","journal-title":"Alcoholism, Clinical and Experimental Research"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01265-w"}],"container-title":["Alcohol, Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.70036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:12:18Z","timestamp":1780474338000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.70036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/acer.70036"],"URL":"https:\/\/doi.org\/10.1111\/acer.70036","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.09.632203","asserted-by":"object"}]},"ISSN":["2993-7175","2993-7175"],"issn-type":[{"value":"2993-7175","type":"print"},{"value":"2993-7175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"2024-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}