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.author Calleja Conde, Javierca
  • dc.contributor.author Echeverry Alzate, Víctorca
  • dc.contributor.author Giné, Elenaca
  • dc.contributor.author Bühler, Kora Mareenca
  • dc.contributor.author Nadal, Roserca
  • dc.contributor.author Maldonado, Rafael, 1961-ca
  • dc.contributor.author Rodríguez de Fonseca, Fernandoca
  • dc.contributor.author Gual, Antonica
  • dc.contributor.author López Moreno, José A.ca
  • dc.date.accessioned 2017-04-26T09:54:56Z
  • dc.date.issued 2016
  • dc.description.abstract BACKGROUND 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.sponsorship This work was supported by The European Foundation for Alcohol Research (to J.A.L.M., F.R.d.F., R.M. and R.N.), the Fondo de Investigación Sanitaria (Red de Trastornos Adictivos, FEDER, RD12/0028/0015 to J.A.L.M., RD12/0028/001 to F.R.d.F., RD12/0028/023 to R.M., RD12/0028/0014 to R.N.) and Ministerio de Ciencia e Innovación (SAF2011-26818 to J.A.L.M.).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Calleja-Conde J, Echeverry-Alzate V, Giné E, Bühler KM, Nadal R, Maldonado R et al. Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood. Br J Pharmacol. 2016 Aug;173(16):2490-505. DOI: 10.1111/bph.13526
  • dc.identifier.doi http://dx.doi.org/10.1111/bph.13526
  • dc.identifier.issn 0007-1188
  • dc.identifier.uri http://hdl.handle.net/10230/30903
  • dc.language.iso eng
  • dc.publisher Wileyca
  • dc.relation.ispartof British Journal of Pharmacology. 2016 Aug;173(16):2490-505
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-26818
  • dc.rights This is the pre-peer reviewed version of the following article: Calleja-Conde J, Echeverry-Alzate V, Giné E, Bühler KM, Nadal R, Maldonado R et al. Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood. Br J Pharmacol. 2016 Aug; 173(16): 2490-505, which has been published in final form at http://dx.doi.org/10.1111/bph.13526. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Opiacis -- Receptors
  • dc.subject.other Alcoholisme
  • dc.subject.other Cocaïna
  • dc.title Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in bloodca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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