Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

Abstract

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.

Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study

“…Moreover, BD might increase the individuals’ risk of making ill-considered decisions about the use of illicit drugs. Finally, co-administration of alcohol and illicit drugs increases the risk of organ damage, especially in young adolescents 28 .…”

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

“…For example, alcohol did not significantly alter heat shock factor 1 (HSF1) (chronic alcohol) (61), Hsp25 (chronic alcohol) (58), Hsp 70 (chronic alcohol) (74), Hsp72 (chronic alcohol) (61), or Hsp90 (acute alcohol) (32). However, lower levels of alcohol intake in male mice increased total and phosphorylated Hsp27 (76). In contrast, work published before 2010 indicated that Hsp 60 and 70 were decreased in hearts from chronic alcohol-fed rats (77, 78).…”

Alcohol Interactions with Psychostimulants: An Overview of Animal and Human Studies

“…MDMA and alcohol exposure in adolescent mice induced physiological and behavioural alteration than either drug administered alone [ 138 ]. In fact, recent study has shown that the co-abuse of MDMA and alcohol exacerbated cardiac cellular stress and toxicity through augmented activation of cardiac sympathetic system in adolescent mice ( Figure 2 ) [ 139 ]. MDMA can induce a rapid release of dopamine and serotonin [ 140 ].…”