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Methamphetamine and MPTP: Similarities and Differences in Mechanisms of Neurotoxic Action

  • Patricia K. Sonsalla
  • Richard E. Heikkila
Part of the Advances in Behavioral Biology book series (ABBI, volume 39)

Abstract

The primary pathophysiological finding in the brains of those afflicted with Parkinson's Disease (PD) is an extensive loss of nigrostriatal dopaminergic neurons within the basal ganglia. Although considerable research has focused on the elucidation of the cause for this neurodegeneration, the substance or mechanism responsible for this neurodegeneration is unknown. A Parkinsonian syndrome can occur in individuals who are exposed acutely to low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; Ballard et al., 1985) or to those exposed chronically to manganese (e.g. manganese miners; see Barbeau, 1984). The symptoms seen in those patients who have ingested toxic quantities of MPTP are nearly identical to those seen in idiopathic PD whereas those seen in humans who have been exposed chronically to high levels of manganese are somewhat different than those in idiopathic PD and may reflect damage not only to nigrostriatal dopaminergic but to other neuronal systems as well. These findings have led to two different hypotheses regarding the etiology of PD. One is that a compound similar in structure or biochemical characteristics to MPTP, derived from exogenous or endogenous sources, is responsible for the neurodegeneration of nigrostriatal dopaminergic neurons in PD. Another is that the oxidation of DA results in the formation of oxygen-derived reactive species (quinones and/or superoxide or the hydroxyl radical) capable of cytotoxicity as is believed to occur in Mn2+ poisoning.

Keywords

Dopaminergic Neuron Neurotoxic Action Tyrosine Hydroxylase Activity Nigrostriatal Dopaminergic Neuron Dopaminergic Neurotoxicity 
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.

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References

  1. Ballard P.A., Tetrud J.W., and Langston J.W. (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP): Seven cases. Neurology 35, 949 – 956.PubMedCrossRefGoogle Scholar
  2. Barbeau A. (1984) Manganese and extrapyramidal disorders. Neurotoxicology 5, 13 – 36.PubMedGoogle Scholar
  3. Buening M.K., and Gibb J.W. (1974) Influence of methamphetamine and neuroleptic drugs on tyrosine hydroxylase activity. Eur.J.Pharmacol. 26, 30 – 34.PubMedCrossRefGoogle Scholar
  4. Burns R.S., Chiueh C.C., Markey S.P., Ebert M.H., Jacobowitz D.M., and Kopin I.J. (1983) A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc.Natl.Acad.Sci.USA 80, 4546 – 4550.PubMedCrossRefGoogle Scholar
  5. Chiba K., Trevor A., and Castagnoli N Jr. (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem.Biophys.Res.Commun. 120, 574 – 578.PubMedCrossRefGoogle Scholar
  6. DeVito M.J., and Wagner G.C. (1989) Methamphetamine-induced neuronal damage: A possible role for free radicals. Neuropharmacology 28, 1145 – 1150.CrossRefGoogle Scholar
  7. Donaldson J. (1987) The physiopathologic significance of manganese in brain: Its relation to schizophrenia and neurodegenerative disorders. Neurotoxicology 8, 451 – 462.PubMedGoogle Scholar
  8. Fuller R.W., and Hemrick-Luecke S.K. (1982) Further studies on the long-term depletion of striatal dopamine in iprindole-treated rats by amphetamine. Neuropharmacology 21, 433 – 438.PubMedCrossRefGoogle Scholar
  9. Fuller R.W., and Hemrick-Luecke S.K. (1985) Mechanisms of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity to striatal dopamine neurons in mice. Prog.Neuropsychopharmacol.Biol.Psychiatry 9, 687 – 690.PubMedCrossRefGoogle Scholar
  10. Heikkila R.E., Hess A., and Duvoisin R.C. (1984a) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-l,2,5,6tetrahydropyridine in mice. Science 224, 1451 – 1453.PubMedCrossRefGoogle Scholar
  11. Heikkila R.E., Manzino L., Cabbat F.S., and Duvoisin R.C. (1984b) Protection against the dopaminergic neurotoxicity of 1-methyl-4 -phenyl -1,2,5,6tetrahydropyridine by monoamine oxidase inhibitors. Nature 311, 467 – 469.PubMedCrossRefGoogle Scholar
  12. Hotchkiss A.J. and Gibb J.W. (1980) Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. J.Pharmacol.Exp.Ther. 214, 257 – 262.PubMedGoogle Scholar
  13. Javitch J.A., D’Amato R.J., Strittmatter S.M., and Snyder S.H. (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc.Natl.Acad.Sci.USA 82, 2173 – 2177.PubMedCrossRefGoogle Scholar
  14. Kopin I.J. (1987) MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson′s Disease. Environ.Health Perspect. 75, 45 – 51.PubMedCrossRefGoogle Scholar
  15. Langston J.W. (1989) Mechanisms underlying neuronal degeneration in Parkinson′s Disease: An experimental and theoretical treatise. Movement Disorders 4, 515 – S25.CrossRefGoogle Scholar
  16. McMillen B.A. (1983) CNS stimulants: two distinct mechanisms of action for amphetamine-like drugs. Trends Pharmacol.Sci. 4, 429 – 432.CrossRefGoogle Scholar
  17. Nicklas W.J., Vyas I., and Heikkila R.E. (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine. Life.Sci. 36, 2503 – 2508.PubMedCrossRefGoogle Scholar
  18. Parenti M., Flauto C., Parati E., Vescovi A., and Groppetti A. (1986) Manganese neurotoxicity: Effects of L-Dopa and pargyline treatments. Brain Res. 367, 8 – 13.PubMedCrossRefGoogle Scholar
  19. Parenti M., Rusconi L., Cappabianca V., Parati E.A., and Groppetti A. (1988) Role of dopamine in manganese neurotoxicity. Brain Res. 473, 236 – 240.PubMedCrossRefGoogle Scholar
  20. Perry T.L., Yong V.W., Clavier R.M., Jones K., Wright J.M., Foulks J.G., and Wall R.A. (1985) Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6tetrahydropyridine by four different antioxidants in the mouse. Neurosci.Lett. 60, 109 – 114.PubMedCrossRefGoogle Scholar
  21. Ramsay R.R., Salach J.I., and Singer T.P. (1986) Uptake of the neurotoxin 1-methyl-4-phenylpyridine (MPP+) by mitochondria and its relation to the inhibition of the mitochondrial oxidation of NAD+-linked substrates by MPP+. Biochem.Biophys.Res.Commun. 134, 743 – 748.PubMedCrossRefGoogle Scholar
  22. Schmidt C.J., and Gibb J.W. (1985) Role of the dopamine uptake carrier in the neurochemical response to methamphetamine: Effects of amfonelic acid. Eur.J.Pharmacol. 109, 73 – 80.PubMedCrossRefGoogle Scholar
  23. Schmidt C.J., Ritter J.K., Sonsalla P.K., Hanson G.R., and Gibb J.W. (1985) Role of dopamine in the neurotoxic effects of methamphetamine. J.Pharmacol.Exp.Ther. 233, 539 – 544.PubMedGoogle Scholar
  24. Schultz W. (1988) MPTP-induced parkinsonism in monkeys: mechanism of action, selectivity and pathophysiology. Gen.Pharmacol. 19, 153 – 161.PubMedCrossRefGoogle Scholar
  25. Seiden L.S., and Vosmer G. (1984) Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single dose of methylamphetamine. Pharmacol. Biochem.Behay. 21, 29 – 31.CrossRefGoogle Scholar
  26. Sonsalla P.K., Gibb J.W., and Hanson G.R. (1986) Roles of D1 and D2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems. J.Pharmacol.Exp.Ther. 238, 932 – 937.PubMedGoogle Scholar
  27. Sonsalla P.K., and Heikkila R.E. (1988) Neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine in several strains of mice. Prog.Neuropsychopharmacol.Biol.Psychiatry 12, 345 – 354.PubMedCrossRefGoogle Scholar
  28. Sonsalla P.K., Nicklas W.J., and Heikkila R.E. (1989) Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity. Science 243, 398 – 400.PubMedCrossRefGoogle Scholar
  29. Steranka L.R. and Rhind A.W. (1987) Effect of cysteine on the persistent depletion of brain monoamines by amphetamine, p-chloroamphetamine and MPTP. Eur.J.Pharmacol. 133, 191 – 197.PubMedCrossRefGoogle Scholar
  30. Sundstrom E., Stromberg I., Tsutsumi T., Olson L., and Jonsson G. (1987) Studies on the effect of 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice. Brain.Res. 405, 26 – 38.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Patricia K. Sonsalla
    • 1
  • Richard E. Heikkila
    • 1
  1. 1.Department of NeurologyUniversity of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical SchoolPiscatawayUSA

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