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Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells

Authors

  • M. T. OLIVEIRA,

    1. Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal
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  • A. C. REGO,

    1. Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal
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  • M. T. MORGADINHO,

    1. Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • T.R. A. MACEDO,

    1. Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • C. R. OLIVEIRA

    Corresponding author
    1. Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal
      Address for correspondence: M.T. Oliveira, Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal. Voice: 351 239 820190; fax: 351 239 822776; mteroliv@cnc.cj.uc.pt.
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Address for correspondence: M.T. Oliveira, Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal. Voice: 351 239 820190; fax: 351 239 822776; mteroliv@cnc.cj.uc.pt.

Abstract

Abstract: Cell death and reactive oxygen species production have been suggested to be involved in neurodegeneration induced by the drugs of abuse. In this study we analyze the toxicity of the following drugs of abuse: heroin, morphine, d-amphetamine, and cocaine in undifferentiated PC12 cells, used as dopaminergic neuronal models. Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (d-amphetamine and cocaine). Toxic effects induced by heroin are associated with a decrease in intracellular dopamine, an increase in DOPAC levels, and the formation of ROS, whereas toxic effects induced by amphetamine are associated with a decrease in intracellular dopamine and in ATP/ADP levels. In contrast with cocaine, both amphetamine and heroin induced features of apoptosis. The data suggest that the death of cultured PC12 cells induced by the drugs of abuse is correlated with a decrease in intracellular dopamine levels, which can be associated with an increased dopamine turnover and oxidative cell injury.

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