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However, there have been no studies regarding the effectiveness of nalmefene when alcohol is used in combination with cocaine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Using operant alcohol self\u2010administration in Wistar rats and qRT\u2010PCR, we evaluated (i) the dose\u2013response curve for s.c. and p.o. nalmefene; (ii) the effects of nalmefene with increasing concentrations of alcohol; (iii) the efficacy of nalmefene on cocaine\u2010potentiated alcohol responding; and (iv) the gene expression profiles of histone deacetylases (<jats:italic>Hdac<\/jats:italic>1\u201311) in peripheral blood <jats:italic>in vivo<\/jats:italic> and in the prefrontal cortex, heart, liver and kidney <jats:italic>post mortem<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>S.c. (0.01, 0.05, 0.1\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) and p.o. (10, 20, 40\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) nalmefene dose\u2010dependently reduced alcohol\u2010reinforced responding by up to 50.3%. This effect of nalmefene was not dependent on alcohol concentration (10, 15, 20%). Cocaine potentiated alcohol responding by approximately 40% and nalmefene (0.05\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) reversed this effect of cocaine. Alcohol increased <jats:italic>Hdac<\/jats:italic> gene expression in blood and nalmefene prevented the increases in <jats:italic>Hdac<\/jats:italic>s 3, 8, 5, 7, 9, 6 and 10. In the other tissues, alcohol and nalmefene either did not alter the gene expression of <jats:italic>Hdac<\/jats:italic>s, as in the prefrontal cortex, or a tissue\u2010<jats:italic>Hdac<\/jats:italic>\u2010specific effect was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Nalmefene might be effective as a treatment for alcohol\u2010dependent patients who also use cocaine. Also, the expression of <jats:italic>Hdacs<\/jats:italic> in peripheral blood might be useful as a biomarker of alcohol use and drug response.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13526","type":"journal-article","created":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T08:52:49Z","timestamp":1464598369000},"page":"2490-2505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nalmefene is effective at reducing alcohol seeking, treating alcohol\u2010cocaine interactions and reducing alcohol\u2010induced histone deacetylases gene expression in blood"],"prefix":"10.1111","volume":"173","author":[{"given":"Javier","family":"Calleja\u2010Conde","sequence":"first","affiliation":[{"name":"Department of Psychobiology, School of Psychology, Campus de Somosaguas Complutense University of Madrid  Madrid 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