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Neurotoxicity, drugs of abuse, and the CuZn-superoxide dismutase transgenic mice

  • Proceedings of the Symposium Cellular and Molecular Mechanisms of Drugs of Abuse Cocaine and Methamphetamine held in Nice, France, August 19–20, 1993
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Abstract

Administration of methamphetamine (METH) to animals causes loss of DA terminals in the brain. The manner by which METH causes these changes in neurotoxicity is not known. We have tested the effects of this drug in copper/zinc (CuZn)-superoxide dismutase transgenic (SOD Tg) mice, which express the human CuZnSOD gene. In nontransgenic (non-Tg) mice, acute METH administration causes significant decreases in DA and dihydroxyphenylacetic acid (DOPAC) in the striata of non-Tg mice. In contrast, there were no significant decreases in striatal DA in the SOD Tg mice. The effects of METH on DOPAC were also attenuated in SOD Tg mice. Chronic METH administration caused decreases in striatal DA and DOPAC in the non-Tg mice, but not in the SOD-Tg mice. Similar studies were carried out with 1-methyl-1,2,3,6-tetrahydropyridine (MPTP), which also causes striatal DA and DOPAC depletion. As in the case of METH, MPTP causes marked depletion of DA and DOPAC in the non-Tg mice, but not in the SOD Tg mice. These results suggest that the mechanisms of toxicity of both METH and MPTP involve superoxide radical formation.

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Authors and Affiliations

  1. Molecular Neuropsychiatry Section, NIH/NIDA, ARC, 21224, Baltimore, MD

    Jean L. Cadet

  2. Neurochemistry Laboratory, Division of Neurotoxicology, NCTR, FDA, 72079, Jefferson, AR

    S. F. Ali

  3. Clinical Psychopharmacology Section, NIH/NIDA, ARC, 21224, Baltimore, MD

    Richard B. Rothman

  4. Department of Pediatrics, University of California, 94143, San Francisco, CA

    Charles J. Epstein

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  1. Jean L. Cadet
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  2. S. F. Ali
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  3. Richard B. Rothman
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  4. Charles J. Epstein
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Cadet, J.L., Ali, S.F., Rothman, R.B. et al. Neurotoxicity, drugs of abuse, and the CuZn-superoxide dismutase transgenic mice. Mol Neurobiol 11, 155–163 (1995). https://doi.org/10.1007/BF02740692

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