RT Journal Article
T1 Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood
A1 Calleja Conde, Javier
A1 Echeverry Alzate, Víctor
A1 Giné Domínguez, Elena
A1 Buhler, Kora Mareen Katharina
A1 Nadal, Roser
A1 Maldonado, Rafael
A1 Rodríguez De Fonseca, Fernando Antonio
A1 Gual, Antoni
A1 López Moreno, José Antonio
AB Background and PurposeThe 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 ApproachUsing 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 ResultsS.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 ImplicationsNalmefene 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.
PB British Pharmacological Society
SN 0007-1188
YR 2016
FD 2016-05-10
LK https://hdl.handle.net/20.500.14352/97777
UL https://hdl.handle.net/20.500.14352/97777
LA eng
NO Calleja-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.
DS Docta Complutense
RD 17 ago 2024