{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:03:32Z","timestamp":1778814212630,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA13475"],"award-info":[{"award-number":["AA13475"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA021142"],"award-info":[{"award-number":["AA021142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>New pharmacotherapies to treat alcohol use disorders (<jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>) are needed. Given the complex nature of <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking\u2010In\u2010the\u2010Dark (<jats:styled-content style=\"fixed-case\">DID<\/jats:styled-content>) paradigm. Active drugs were studied further using the dose\u2013response relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult female and male C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice were singly housed and the <jats:styled-content style=\"fixed-case\">DID<\/jats:styled-content> paradigm was performed using 20% EtOH over a 4\u2010day period. Mice were administered a tetracycline or its vehicle 20\u00a0hours prior to drinking. Water and EtOH consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for EtOH content measurement immediately following the final bout of drinking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven tetracyclines were tested at a 50\u00a0mg\/kg dose. Only minocycline and tigecycline significantly reduced EtOH drinking, and doxycycline showed a strong effect size trend toward reduced drinking. Subsequent studies with these 3 drugs revealed a dose\u2010dependent decrease in EtOH consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on EtOH drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in EtOH consumption was minocycline\u00a0&gt;\u00a0doxycycline\u00a0&gt;\u00a0tigecycline, indicating efficacy was not strictly related to their partition coefficients or distribution constants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Due to its effectiveness in reducing high EtOH consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13253","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T16:38:19Z","timestamp":1479314299000},"page":"2482-2490","source":"Crossref","is-referenced-by-count":23,"title":["Effective Reduction in High Ethanol Drinking by Semisynthetic Tetracycline Derivatives"],"prefix":"10.1111","volume":"40","author":[{"given":"Peter J.","family":"Syapin","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick C.","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clayton L.","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Groot","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Baby","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazan M.","family":"Al\u2010Hasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael","family":"Segura\u2010Ulate","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Scheible","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"},{"name":"Department of Pharmacology University of Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy T.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Luis","family":"Redondo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R. M.","family":"Trotter","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Bergeson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center Lubbock Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12288"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/26.3.347"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13252"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13251"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.06.026"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2010.00284.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00216-6"},{"key":"e_1_2_6_11_1","unstructured":"CDC(2014)Excessive Drinking Costs U.S. $223.5 Billion. Available at:http:\/\/www.cdc.gov\/features\/alcoholconsumption\/. Accessed on November 16 2015."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00004-X"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.2.232-260.2001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00010-5"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3906-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12639"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00003-8"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803590"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00379.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12139"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.320.5878.862"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2012.04054.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.09.006"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13259"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152710790966641"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840090302"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2012.012029"},{"key":"e_1_2_6_28_1","unstructured":"2009 NIAAA NIAAA Rethinking Drinking Alcohol and Your Health"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.11.4.561"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05298.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.8.1829"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.1997.58.7"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00002-6"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4053"},{"key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.15288\/jsads.2014.75.79","article-title":"Pharmacotherapy of alcohol use disorders: seventy\u2010five years of progress","volume":"75","author":"Zindel LR","year":"2014","journal-title":"J Stud Alcohol Drugs"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.13253","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.13253","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.13253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T12:32:49Z","timestamp":1695040369000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.13253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,14]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1111\/acer.13253"],"URL":"https:\/\/doi.org\/10.1111\/acer.13253","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,14]]}}}