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Adolescent pre-exposure to ethanol and 3,4-methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug-induced reinstatement

Authors

  • Bruno Ribeiro Do Couto,

    1. Departamento de Anatomía Humana y Psicobiología, Facultad de Psicología, Universidad de Murcia, Campus Universitario de Espinardo, Spain
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  • Manuel Daza-Losada,

    1. Departamento de Psicobiologia, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, Universidad de Valencia, Spain
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  • Marta Rodríguez-Arias,

    1. Departamento de Psicobiologia, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, Universidad de Valencia, Spain
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  • Roser Nadal,

    1. Unitat de Psicobiologia and Institut de Neurociencies, Universitat Autonoma de Barcelona, Spain
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  • Consuelo Guerri,

    1. Laboratorio de Patología Celular, Centro de Investigación Príncipe Felipe, Valencia, Spain
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  • Teresa Summavielle,

    1. Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Portugal
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  • Jose Miñarro,

    1. Departamento de Psicobiologia, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, Universidad de Valencia, Spain
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  • Maria A. Aguilar

    Corresponding author
    1. Departamento de Psicobiologia, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, Universidad de Valencia, Spain
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Maria A. Aguilar, Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010 Valencia, Spain. E-mail: asuncion.aguilar@uv.es

ABSTRACT

Many adolescents often take ethanol (EtOH) in combination with 3,4-methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre-exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre-exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre-treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre-exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups with a priming dose of 2.5 mg/kg of MDMA, in the groups pre-exposed to EtOH or MDMA alone with a priming dose of 1.25 mg/kg, and in the groups pre-treated with MDMA alone with a priming dose of 0.625 mg/kg. Pre-treatment during adolescence with MDMA or EtOH induced long-term changes in the level of biogenic amines [dihydroxyphenyl acetic acid, homovanillic acid, dopamine turnover, serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the striatum, and 5-HT and 5-HIAA in the cortex] after the first reinstatement test, although these effects depended on the dose used during conditioning. These results suggest that exposure to EtOH and MDMA during adolescence reinforces the addictive properties of MDMA.

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