The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice

• Published in: Toxicology and applied pharmacology 2016-02, Vol.293, p.10-20
• Main Authors: Ciudad-Roberts, Andrés, Duart-Castells, Leticia, Camarasa, Jorge, Pubill, David, Escubedo, Elena
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Adolescence; ADOLESCENTS; Alcohol; AMPHETAMINES; Animals; Brain - cytology; Brain - drug effects; Brain - metabolism; CATALASE; Catalase - metabolism; Cathinones; DEOXYURIDINE; DOPAMINE; Dopamine Plasma Membrane Transport Proteins - metabolism; Drug Interactions; ETHANOL; Ethanol - toxicity; GLUTATHIONE; Glutathione Peroxidase - metabolism; HIPPOCAMPUS; HYDROXYLASES; Lipid Peroxidation - drug effects; Male; Malondialdehyde - metabolism; Maze Learning - drug effects; Memory - drug effects; Mephedrone; Methamphetamine - analogs & derivatives; Methamphetamine - toxicity; MICE; Neurogenesis; Neurogenesis - drug effects; Neurotoxicity; SEROTONIN; Serotonin Plasma Membrane Transport Proteins - metabolism; Street Drugs - toxicity; SUPEROXIDE DISMUTASE; TRYPTOPHAN; Tryptophan Hydroxylase - metabolism; TYROSINE; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2015.12.019

A new family of psychostimulants, under the name of cathinones, has broken into the market in the last decade. In light of the fact that around 95% of cathinone consumers have been reported to combine them with alcoholic drinks, we sought to study the consequences of the concomitant administration of ethanol on mephedrone ­induced neurotoxicity. Adolescent male Swiss­CD1 mice were administered four times in one day, every 2h, with saline, mephedrone (25mg/kg), ethanol (2; 1.5; 1.5; 1g/kg) and their combination at a room temperature of 26±2°C. The combination with ethanol impaired mephedrone­induced decreases in dopamine transporter and tyrosine hydroxylase in the frontal cortex; and in serotonin transporter and tryptophan hydroxylase in the hippocampus by approximately 2­fold, 7days post­treatment. Furthermore, these decreases correlated with a 2­fold increase in lipid peroxidation, measured as concentration of malondialdehyde (MDA), 24h post-treatment, and were accompanied by changes in oxidative stress-related enzymes. Ethanol also notably potentiated mephedrone-induced negative effects on learning and memory, as well as hippocampal neurogenesis, measured through the Morris water maze (MWM) and 5-bromo-2′-deoxyuridine staining, respectively. These results are of special significance, since alcohol is widely co­abused with amphetamine derivatives such as mephedrone, especially during adolescence, a crucial stage in brain maturation. Given that the hippocampus is greatly involved in learning and memory processes, normal brain development in young adults could be affected with permanent behavioral consequences after this type of drug co-abuse. [Display omitted] •Mice were administered a binge regimen of mephedrone plus/minus ethanol.•Ethanol exacerbated mephedrone-induced changes in 5-HT and DA function markers.•Neurochemical alterations were accompanied by an increase in oxidative stress.•Ethanol potentiated mephedrone-induced learning deficits and decreased neurogenesis.