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

Ethanol and MDMA, two widely abused recreational drugs, cause oxidative stress in the brain. In adolescent CD1 mice, acute MDMA treatment, alone or combined with ethanol, produced significant protein oxidative damage specifically in the hippocampus, but not in the prefrontal cortex, 72 hours after treatment. The damaged proteins are involved in energy metabolism, structural function, axonal outgrowth and stability, and neurotransmitter release. MDMA-treated mice showed greater oxidative damage than ethanol-only mice. While ethanol did not impair radial arm maze acquisition, MDMA impaired long-term declarative memory in both the object recognition assay and the radial arm maze, suggesting that MDMA-induced oxidative damage to hippocampal proteins contributes to memory deficits.

Study at a glance

Abstract

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 CD 1 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.