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Prior in vivo and in vitro studies suggest that corticosteroids, in particular, may be elevated during<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>intoxication and withdrawal, suggesting that intracellular glucocorticoid receptors (<jats:styled-content style=\"fixed-case\">GRs<\/jats:styled-content>) may promote the development of<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>dependence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult male<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats were subjected to a 4\u2010day binge\u2010like EtOH administration regimen (3 to 5\u00a0g\/kg\/i.g. every 8\u00a0hours designed to produce peak blood EtOH levels (BELs) of &lt;300\u00a0mg\/dl). Subgroups of animals received s.c. injection of the GR antagonist mifepristone (20 or 40\u00a0mg\/kg in peanut oil at 0800\u00a0hours on each of the 4\u00a0days prior to withdrawal).<jats:styled-content style=\"fixed-case\">BELs<\/jats:styled-content>were assessed at 0900 and 1500\u00a0hours on Days 2 (D2) and 4 (D4) of the regimen.<jats:styled-content style=\"fixed-case\">BEL<\/jats:styled-content>, blood corticosterone levels (<jats:styled-content style=\"fixed-case\">BCLs<\/jats:styled-content>), and<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>withdrawal\u2013associated behavioral abnormalities were assessed 10 to 12\u00a0hours after the final<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Daily mean<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>doses for D1 to D4 of the regimen were 14.4, 9.9, 7.1, and 8.6\u00a0g\/kg, respectively. The<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>gavage regimen produced mean<jats:styled-content style=\"fixed-case\">BEL<\/jats:styled-content>s of 255\u00a0mg\/dl at 0900 on D2 and 156.2\u00a0mg\/dl at 0900 on D4 of the regimen. Withdrawal from the<jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>exposure regimen, beginning 10\u00a0hours after the last EtOH administration, produced significant elevations in<jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>and behavioral abnormalities including tremors, stereotypy, and \u201cwet dog shakes.\u201d Mifepristone administration did not alter food intake or weight during the 4\u2010day regimen, nor were there drug\u2010dependent differences in<jats:styled-content style=\"fixed-case\">BEL<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>on withdrawal day. Although mifepristone produced no significant changes in behavior of EtOH\u2010na\u00efve animals, pretreatment with mifepristone (40\u00a0mg\/kg) significantly reduced the severity of EtOH withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Findings suggest that activation of GRs promotes neuroadaptation to binge\u2010like EtOH exposure, contributing to the development of EtOH dependence. Further, GRs may represent therapeutic targets to be exploited in reducing the severity of EtOH withdrawal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12093","type":"journal-article","created":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T16:08:50Z","timestamp":1364227730000},"page":"1417-1423","source":"Crossref","is-referenced-by-count":37,"title":["Mifepristone Pretreatment Reduces Ethanol Withdrawal Severity In Vivo"],"prefix":"10.1111","volume":"37","author":[{"given":"Lynda","family":"Sharrett\u2010Field","sequence":"first","affiliation":[{"name":"Department of Psychology, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy R.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Psychology, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer N.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Psychology, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Psychology, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Prendergast","sequence":"additional","affiliation":[{"name":"Department of Psychology, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000084161"},{"key":"e_1_2_6_3_1","first-page":"67","article-title":"Disturbances of the stress response: the role of the HPA axis during alcohol withdrawal and abstinence","volume":"22","author":"Adinoff B","year":"1998","journal-title":"Alcohol Health Res World"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000176356.97620.84"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.107896"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4530(89)90043-7"},{"key":"e_1_2_6_7_1","first-page":"318","article-title":"Alcohol\u2010induced Cushing syndrome. 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