4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

Authors

  • Ramón Sotomayor-Zárate,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
    2. Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
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  • Gabriel Quiroz,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Katherine A. Araya,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Jorge Abarca,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • María R. Ibáñez,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Alejandro Montecinos,

    1. Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile
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  • Carlos Guajardo,

    1. Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile
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  • Gabriel Núñez,

    1. PhD Program in Biotechnology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile
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  • Angélica Fierro,

    1. Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile
    2. Millennium Institute for Cell Dynamics and Biotechnology, Santiago, Chile
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  • Pablo R. Moya,

    1. Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA
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  • Patricio Iturriaga-Vásquez,

    1. Millennium Institute for Cell Dynamics and Biotechnology, Santiago, Chile
    2. Department of Chemistry, Faculty of Sciences, University of Chile, Santiago, Chile
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  • Cristóbal Gómez-Molina,

    1. Department of Chemistry, Faculty of Sciences, University of Chile, Santiago, Chile
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  • Katia Gysling,

    1. Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Miguel Reyes-Parada

    Corresponding author
    1. Millennium Institute for Cell Dynamics and Biotechnology, Santiago, Chile
    2. Faculty of Medical Sciences, School of Medicine, University of Santiago de Chile, Santiago, Chile
    3. Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile
    • Millennium Science Nucleus in Stress and Addiction and Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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Author for correspondence: Miguel Reyes-Parada, Faculty of Medical Sciences, University of Santiago de Chile, Av. Alameda 3363, Estación Central, Santiago, Chile (Tel/fax +56-2-7183526, e-mail miguel.reyes@usach.cl).

Abstract

4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 μM) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.

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