Memory impairment and hippocampus specific protein oxidation induced by ethanol intake and 3, 4-Methylenedioxymethamphetamine (MDMA) in mice

Abstract

Ethanol and 3, 4-Methylenedioxymethamphetamine (MDMA) are popular recreational drugs widely abused by adolescents that may induce neurotoxic processes associated with behavioural alterations. Adolescent CD1 mice were subjected to ethanol intake using the drinking in the dark (DID) procedure, acute MDMA or a combination. Considering that both drugs of abuse cause oxidative stress in the brain, protein oxidative damage in different brain areas was analysed 72 h after treatment using a proteomic approach. Damage to specific proteins in treated animals was significant in the hippocampus but not in the prefrontal cortex. The damaged hippocampus proteins were then identified by mass spectrometry, revealing their involvement in energy metabolism, structural function, axonal outgrowth and stability, and neurotransmitter release. Mice treated with MDMA displayed higher oxidative damage than ethanol-treated mice. To determine whether this oxidative damage was affecting hippocampus activity, declarative memory was evaluated at 72 h after treatment using the object recognition assay and the radial arm maze. Although acquisition in the radial arm maze was not impaired by ethanol intake, MDMA treatment impaired long-term memory in both tests. Therefore, oxidative damage to specific proteins observed under MDMA treatment affects important cellular function on the hippocampus that may contribute to declarative memory deficits. Ethanol and MDMA are two commonly co-abused drugs among adolescents with detrimental side effects. Oxidative stress is induced by these drugs of abuse and can damage specific proteins and affect important cellular functions in brains of consumers. Our findings reveal that specific hippocampus proteins are oxidatively damaged and memory processes are affected. Our findings reveal that specific hippocampus proteins are oxidatively damaged after ethanol and MDMA administration and memory processes are affected. © 2013 International Society for Neurochemistry.