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The goals of the present studies were to identify male and female mice with prior binge drinking experience that exhibited sensitivity and resilience to PS\u2010enhanced drinking and then to test two target molecules (corticotropin releasing factor receptor 1 [CRF\u2010R1] antagonist NBI\u201027914 [NBI] and G\u2010protein coupled receptor 39 [GPR39] agonist TC\u2010G 1008 [TC\u2010G]) for their ability to selectively reduce PS\u2010enhanced drinking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult male and female C57BL\/6J mice received seven binge ethanol sessions, a period of abstinence, and acclimation to lickometer chambers to examine the effects of NBI or TC\u2010G on stress\u2010associated drinking. Following establishment of stable baseline (BL) drinking and four intermittent PS exposures, mice were classified into \u201cSensitive\u201d and \u201cResilient\u201d subgroups, based on the change in ethanol drinking from BL after PS2\u20104. Then, mice received injections of vehicle or drug (NBI or TC\u2010G) in a within\u2010subjects design. Control studies examined the effects of NBI or TC\u2010G on binge drinking, locomotor activity, and saccharin intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NBI and TC\u2010G significantly suppressed binge drinking in male and female mice in the control studies. However, sensitivity to the ability of the compounds to decrease PS\u2010enhanced drinking did not differ between animals in the \u201cPS\u2010sensitive\u201d versus \u201cPS\u2010resilient\u201d subgroups, and female mice were insensitive to TC\u2010G in the traumatic stress drinking model. Specifically, NBI doses of 5 and 10\u2009mg\/kg (males) and 12.5\u2009mg\/kg (females) significantly decreased PS\u2010associated drinking in both subgroups. TC\u2010G (7.5\u2009mg\/kg) significantly decreased PS\u2010associated drinking in both subgroups of male mice but not in female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present findings suggest that stress sensitivity and subsequent enhanced ethanol drinking in the \u201cSensitive\u201d subgroup may not increase sensitivity to CRF\u2010R1 antagonism or GPR39 agonism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70005","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:04:03Z","timestamp":1741770243000},"page":"866-882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Traumatic stress\u2010enhanced ethanol drinking: Sex, but not stress responsivity, alters sensitivity to the effects of a <scp>CRF<\/scp>\u2010<scp>R1<\/scp> antagonist and a <scp>GPR39<\/scp> agonist in mice"],"prefix":"10.1111","volume":"49","author":[{"given":"Melinda L.","family":"Helms","sequence":"first","affiliation":[{"name":"Department of Research (R&amp;D\u201049) VA Portland Health Care System  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Finn","sequence":"additional","affiliation":[{"name":"Department of Research (R&amp;D\u201049) VA Portland Health Care System  Portland Oregon USA"},{"name":"Department of Behavioral Neuroscience (L\u2010470) Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A.","family":"Nipper","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience (L\u2010470) Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey E.","family":"Ryabinin","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience (L\u2010470) Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0001-3640","authenticated-orcid":false,"given":"Rita P.","family":"Cervera\u2010Juanes","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Center for Precision Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108045"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2022.834880"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP0000000000000460"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.03.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011163"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.266"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilu006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2014.07.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010018\u20100308\u20101"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.11.019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2018.12.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010023\u201004766\u2010z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.70"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2023.101094"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010004\u20102039\u20108"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40429\u2010023\u201000540\u20100"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00325"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2018.02.004"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530\u20100277.2007.00379.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.alc.0000179413.82308.6b"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12076"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.2161"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13859"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2013.11.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.04.016"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1392\u201015.2015"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22749"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1018\/10253890.2018.1484099"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2018.02.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010020\u201005659\u2010w"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.05.007"},{"key":"e_1_2_8_33_1","unstructured":"NIAAA. 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