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

Authors

  • Clara Ros-Simó,

    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain
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  • Maria Moscoso-Castro,

    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain
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  • Jéssica Ruiz-Medina,

    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain
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  • Joaquim Ros,

    1. Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, Lleida, Spain
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  • Olga Valverde

    Corresponding author
    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain
    • Address correspondence and reprint requests to Olga Valverde, MD, PhD, Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/ Dr. Aiguader, 88, 08003 Barcelona, Spain. E-mail: olga.valverde@upf.edu

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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.

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