Neuropsychopharmacologic and neurotoxicologic effects of the combination of ethanol with mephedrone in adolescent mice

Abstract

In the last decade, a new family of synthetic psychostimulant drugs, under the name of cathinones, broke into the market. These drugs are mainly consumed by adolescents and young adults with recreational purposes, in most cases combined with alcoholic drinks. Although a number of works about new cathinones have been recently published, none explored the consequences of such combination. Because adolescence is a crucial period in brain development, we sought to study the effects of the combination of mephedrone plus ethanol in adolescent mice, focusing on psychostimulant and conditioning effects, as well as on neurotoxicity markers. Ethanol increased both locomotor activity and conditioned place preference (CPP) induced by mephedrone. RNA microarray assays after CPP test yielded significant alterations in neuronal plasticity-related genes and a key role of BDNF and dopamine D3 receptors in CPP acquisition was found. Ethanol potentiated the oxidative stress as well as the decreases in dopaminergic and serotonergic markers in frontal cortex and hippocampus respectively, after a binge treatment with mephedrone. Moreover, the drug combination impaired spatial learning and memory, as well as neurogenesis to a higher extent than mephedrone alone.