Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood

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dc.contributor.authorCalleja Conde, Javier
dc.contributor.authorEcheverry Alzate, Víctor
dc.contributor.authorGiné Domínguez, Elena
dc.contributor.authorBuhler, Kora Mareen Katharina
dc.contributor.authorNadal, Roser
dc.contributor.authorMaldonado, Rafael
dc.contributor.authorRodríguez De Fonseca, Fernando Antonio
dc.contributor.authorGual, Antoni
dc.contributor.authorLópez Moreno, José Antonio
dc.date.accessioned2024-02-01T13:47:31Z
dc.date.available2024-02-01T13:47:31Z
dc.date.issued2016-05-10
dc.description.abstractBackground and Purpose The opioid antagonist nalmefene (selincro®) was approved for alcohol-related disorders by the European Medicines Agency in 2013. However, there have been no studies regarding the effectiveness of nalmefene when alcohol is used in combination with cocaine. Experimental Approach Using operant alcohol self-administration in Wistar rats and qRT-PCR, we evaluated (i) the dose–response 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-potentiated alcohol responding; and (iv) the gene expression profiles of histone deacetylases (Hdac1–11) in peripheral blood in vivo and in the prefrontal cortex, heart, liver and kidney post mortem. Key Results S.c. (0.01, 0.05, 0.1 mg·kg−1) and p.o. (10, 20, 40 mg·kg−1) nalmefene dose-dependently reduced alcohol-reinforced 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 mg·kg−1) reversed this effect of cocaine. Alcohol increased Hdac gene expression in blood and nalmefene prevented the increases in Hdacs 3, 8, 5, 7, 9, 6 and 10. In the other tissues, alcohol and nalmefene either did not alter the gene expression of Hdacs, as in the prefrontal cortex, or a tissue-Hdac-specific effect was observed. Conclusions and Implications Nalmefene might be effective as a treatment for alcohol-dependent patients who also use cocaine. Also, the expression of Hdacs in peripheral blood might be useful as a biomarker of alcohol use and drug response.
dc.description.departmentDepto. de Psicobiología y Metodología en Ciencias del Comportamiento
dc.description.facultyFac. de Psicología
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationCalleja-Conde, J., Echeverry-Alzate, V., Giné, E., Bühler, K. -M., Nadal, R., Maldonado, R., Rodríguez de Fonseca, F., Gual, A., and López-Moreno, J. A. (2016) Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood. British Journal of Pharmacology, 173: 2490–2505. doi: 10.1111/bph.13526.
dc.identifier.doi10.1111/bph.13526
dc.identifier.essn1476-5381
dc.identifier.issn0007-1188
dc.identifier.officialurlhttps://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13526
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97777
dc.journal.titleBritish Journal of Pharmacology
dc.language.isoeng
dc.page.final2505
dc.page.initial2490
dc.publisherBritish Pharmacological Society
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco2403 Bioquímica
dc.subject.unesco3209 Farmacología
dc.subject.unesco61 Psicología
dc.titleNalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood
dc.typejournal article
dc.type.hasVersionVoR
dspace.entity.typePublication
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