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Science 20 January 1989:
Vol. 243. no. 4889, pp. 398 - 400
DOI: 10.1126/science.2563176
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Articles

Science, Vol 243, Issue 4889, 398-400
Copyright © 1989 by American Association for the Advancement of Science

articles

Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity

PK Sonsalla, WJ Nicklas, and RE Heikkila

Department of Neurology, University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School, Piscataway 08854.

The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.


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