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Using the reinstatement model, we have shown that corticotropin\u2010releasing factor (<jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content>) underlies stress\u2010induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with <jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content> in these effects. Dynorphin and its receptor (kappa opioid receptor, <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content>) are involved in stress responses and in alcohol seeking. <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content> R) may interact in the production of stress\u2010related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Long Evans rats were trained to self\u2010administer alcohol (12% w\/v). After extinction of responding, we determined the effects of the <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content> agonist, U50,488 (2.5, 5\u00a0mg\/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content> antagonist nor\u2010binaltorphimine dihydrochloride (nor\u2010<jats:styled-content style=\"fixed-case\">BNI<\/jats:styled-content>) (10\u00a0mg\/kg) administered at different times before U50,488. We then examined the effects of nor\u2010<jats:styled-content style=\"fixed-case\">BNI<\/jats:styled-content> on reinstatement induced by the stressor yohimbine (1.25\u00a0mg\/kg) and on reinstatement induced by exposure to alcohol\u2010associated cues . Finally, we determined whether <jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content> R1 blockade with antalarmin (10, 20\u00a0mg\/kg) attenuates alcohol seeking induced by U50,488.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>U50,488 reinstated alcohol seeking. Prior treatment with nor\u2010<jats:styled-content style=\"fixed-case\">BNI<\/jats:styled-content> 2, but not 24\u00a0h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue\u2010induced reinstatement was blocked by nor\u2010<jats:styled-content style=\"fixed-case\">BNI<\/jats:styled-content> administered 2\u00a0h prior to testing. Finally, U50,488\u2010induced reinstatement was blocked by antalarmin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data further support a role for <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content> in reinstatement of alcohol seeking under nonstress and stressful conditions and that <jats:styled-content style=\"fixed-case\">KOR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CRF<\/jats:styled-content> R interact in these effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.222","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T11:47:54Z","timestamp":1392637674000},"page":"356-367","source":"Crossref","is-referenced-by-count":66,"title":["The role of kappa opioid receptors in stress\u2010induced reinstatement of alcohol seeking in rats"],"prefix":"10.1002","volume":"4","author":[{"given":"Douglas","family":"Funk","sequence":"first","affiliation":[{"name":"Neurobiology of Alcohol Laboratory Centre for Addiction and Mental Health Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Coen","sequence":"additional","affiliation":[{"name":"Neurobiology of Alcohol Laboratory Centre for Addiction and Mental Health Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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