{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:03:09Z","timestamp":1779901389168,"version":"3.53.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K24AA025704"],"award-info":[{"award-number":["K24AA025704"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R21AA029771"],"award-info":[{"award-number":["R21AA029771"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["F32AA029288"],"award-info":[{"award-number":["F32AA029288"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA029701\u201001S1"],"award-info":[{"award-number":["R01AA029701\u201001S1"]}],"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Despite increasing attention to the neurobiology of alcohol use disorder (AUD), development of effective pharmacotherapies remains limited. Many medications with promising preclinical profiles fail to translate into clinical efficacy. This scoping review characterizes preclinical studies evaluating medications for AUD that have also been tested in human laboratory paradigms or clinical trials. We focus on two widely used paradigms: the two\u2010bottle choice (2\n                    <jats:sc>BC<\/jats:sc>\n                    ) task, which measures alcohol consumption and preference, and operant reinstatement models, which capture relapse\u2010like behavior. A systematic search and data extraction identified preclinical studies using 2\n                    <jats:sc>BC<\/jats:sc>\n                    and reinstatement paradigms to evaluate medications that progressed to human testing. Study characteristics (species, strain, sex, outcomes, and sample sizes) were recorded and effect sizes (corrected Cohen's\n                    <jats:italic>d<\/jats:italic>\n                    ) were summarized across outcome domains. Ninety\u2010two unique studies met criteria: 74 employing the 2\n                    <jats:sc>BC<\/jats:sc>\n                    paradigm and 18 using operant reinstatement models, including 1731 animals. Rats were the most common species and sex bias was pronounced: 77 2\n                    <jats:sc>BC<\/jats:sc>\n                    studies using only males, five only females, and all 18 reinstatement studies used male rats exclusively. For 2\n                    <jats:sc>BC<\/jats:sc>\n                    consumption, the largest effects were observed for medications with limited studies, such as levetiracetam (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22124.58), while more extensively tested medications showed moderate effects, including prazosin (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.74) and naltrexone (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.63). For 2\n                    <jats:sc>BC<\/jats:sc>\n                    preference, levetiracetam again showed a large effect in a single study (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22124.29). In reinstatement models, rimonabant showed the largest effect (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22123.11), while naltrexone (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.70), baclofen (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22121.05), and varenicline (\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u2009\u22120.72) had moderate effects. This review highlights substantial heterogeneity in study design and underutilization of reinstatement and female animals. Medications with moderate, replicable preclinical effects, especially those tested across both 2\n                    <jats:sc>BC<\/jats:sc>\n                    and reinstatement models, may hold greater translational promise. These findings offer key opportunities for enhancing the translational alignment of preclinical AUD pharmacotherapy research.\n                  <\/jats:p>","DOI":"10.1111\/acer.70287","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:02:02Z","timestamp":1778252522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Scoping Review of Preclinical Paradigms for Clinically Tested Medications in Alcohol Use Disorder"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-5211","authenticated-orcid":false,"given":"Steven J.","family":"Nieto","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurosciences Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Department of Psychology University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanna","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wave\u2010Ananda","family":"Baskerville","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-7796","authenticated-orcid":false,"given":"Kaitlin R.","family":"McManus","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo F.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-6957","authenticated-orcid":false,"given":"Howard C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-9444","authenticated-orcid":false,"given":"Lara A.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California at Los Angeles  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California at Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011163"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.02.004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010021\u201001670\u20103"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2014.01.006"},{"key":"e_1_2_8_6_1","first-page":"71","volume-title":"Handbook of Clinical Neurology","author":"Crabbe J. 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