Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress.
Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.
Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.
Javier
J
Navarro-Zaragoza
Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu Fabra, Barcelona, Spain.
Clara
C
Ros-Simó
Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.
María-Victoria
MV
Milanés
Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu Fabra, Barcelona, Spain.
Olga
O
Valverde
Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.
María-Luisa
ML
Laorden
D000818:Animals; D063425:Binge Drinking; D066126:Cardiotoxicity; D000431:Ethanol / Q000633:toxicity*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D009647:Normetanephrine / Q000378:metabolism; D010766:Phosphorylation; D013312:Stress, Physiological / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; D009647:Normetanephrine; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine