Advertisement

Neurotoxicity of Drugs of Abuse

  • Jean Lud Cadet

Abstract

The amphetamines are drugs of abuse that are presently seeing a significant resurgence. In California, it has been suggested that methamphetamine (METH) will surpass cocaine as the preferential drug of abuse. This might be related to the relative ease of its synthesis and the focus of government agencies on cocaine. Unlike cocaine, the amphetamines are, however, known causes of major neurotoxic damage to mammalian monoaminergic systems (1–3) For example, METH depletes dopamine (DA) and its metabolites (1,2,4,5), depletes DA uptake sites (1,6) and causes marked decreases in tyrosine hydroxylase (TH) activity in the nigrostriatal DA system. METH can also cause significant alterations in the serotonin (5-HT) system depending on the doses of the drug used in the experiments. In contrast to the effects of METH, another closely related analog, methyldioxymethamphetamine (MDMA, “ecstasy”) exerts most of its effects on the serotoninergic system of most mammals (including humans) except in mice, where MDMA affects mainly the dopaminergic system (2,7).

Keywords

Nitric Oxide Tyrosine Hydroxylase Down Syndrome Nicotinamide Adenine Dinucleotide Dialuric Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ricaurte GA, Schuster CR, Seiden LS. Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: regional study. Brain Res 1980, 193: 153–163.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Callaghan JP, Miller DB. Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse. J Pharmacol Exp Ther 1994, 270: 741–751.PubMedGoogle Scholar
  3. 3.
    Steranka LR, Sanders-Bush E. Long-term effects of continuous exposure to amphetamine in brain dopamine concentration and synaptosomal uptake in mice. Eur J Pharmacol 1980, 65: 439–443.PubMedCrossRefGoogle Scholar
  4. 4.
    Cadet JL., Ladenheim B, Baum I, Carlson E, Epstein C. CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetaine (MDMA). Brain Res 1994a, 655: 259–262.PubMedCrossRefGoogle Scholar
  5. 5.
    Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller RJ, Westley J. Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res 1980, 181: 151–160.PubMedCrossRefGoogle Scholar
  6. 6.
    Nakayama M, Koyama T, Yamashita I. Long-lasting decreases in dopamine uptake sites following repeated administration of methamphetamine in the rat striatum. Brain Res 1992, 601: 209–212.CrossRefGoogle Scholar
  7. 7.
    Cadet JL, Ladenheim B, Hirata H, Rothman RB, Ali RB, Carlson E, Epstein C, Moran TH. Superoxide radicals mediate the biochemical effects of methylendioxymethamphetamine (MDMA): evidence from using CuZn-superoxide transgenic mice. Synapse 1995, 21: 169–175.PubMedCrossRefGoogle Scholar
  8. 8.
    Marshall JF, O’Dell SJ, Weihmuller FB. Dopamine-glutamate interactions in methaphetamine-induced neurotoxicity. J Neural Transm 1993, 91: 241–254.CrossRefGoogle Scholar
  9. 9.
    Cadet JL. A unifying hypothesis of movement and madness: involvement of free radicals in disorders of the isodendritic core. Med Hypotheses 1988, 27: 87–94.CrossRefGoogle Scholar
  10. 10.
    Cohen G, Heikkila RE. The generation of hydrogen peroxide, Superoxide radical and hydroxyl radical by hydroxydopamine, dialuric acid, and related cytotoxic agents. J Biol Chem 1974, 249: 2447–2452.PubMedGoogle Scholar
  11. 11.
    De Vito MJ, Wagner GC Methamphetamine-induced neuronal damage: A possible role for free radicals. Neuropharmacology 1989, 28: 1145–1150.PubMedCrossRefGoogle Scholar
  12. 12.
    Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993, 262: 689–695.PubMedCrossRefGoogle Scholar
  13. 13.
    Dawson VL, Dawson TM, Bartley DA, Uhi GR, Snyder SH Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 1993, 13: 2651–2661.PubMedGoogle Scholar
  14. 14.
    Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991, 43: 109–142.PubMedGoogle Scholar
  15. 15.
    Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992, 6: 3051–3064.PubMedGoogle Scholar
  16. 16.
    Beckman JS. The double-edged role of nitric oxide in brain and superoxide-mediated injury. J Develop Physiol 1991, 15: 53–59.Google Scholar
  17. 17.
    Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of Superoxide and nitric oxide. Arch Biochem Biophys 1991, 288: 481–487.PubMedCrossRefGoogle Scholar
  18. 18.
    Sheng P, Cerutti C, Cadet JL. Methamphetamine (METH) causes reactive gliosis in vitro: attenuation by the ADP-ribosylation (ADPR) inhibitor, benzamide. Life Sciences 1994, 55: 51–54.CrossRefGoogle Scholar
  19. 19.
    Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG. Oxidant injury of cells: DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986a, 77: 1312–1320.PubMedCrossRefGoogle Scholar
  20. 20.
    Schraufstatter JU, Hyslop PA, Minshaw DB, Spragg RG, Sklar LA, Cochrane CG. Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly (ADP-ribose) polymerase. Proc Natl Acad Sci USA 1986b, 83: 4908–4912.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly(ADP-Ribose) synthetase in neurotoxicity. Science 1994, 263: 687–689.PubMedCrossRefGoogle Scholar
  22. 22.
    Hirata H, Cadet JL. P53 knockout mice are protected against the longterm effects of methamphetamine on dopaminergic terminals and cell bodies. J Neuro chem 1997, 69: 780–790.Google Scholar
  23. 23.
    Cadet JL, Ordonez SV, Ordonez JV. Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2. Synapse 1997, 25: 176–184.PubMedCrossRefGoogle Scholar
  24. 24.
    Epstein CJ, Avraham KB, Lovett M, Smith S, Elroy-Stein O, Rotman G, et al. Transgenic mice with increased CuZn-superoxide dismutase activity: Animal model of dosage effects in Down Syndrome. Proc Natl Acad Sci USA 1997, 84: 8044–8048.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Jean Lud Cadet

There are no affiliations available

Personalised recommendations