Role for Excitatory Amino Acids in Methamphetamine-Induced Nigrostriatal Dopaminergic Toxicity

• Published in: Science (American Association for the Advancement of Science) Vol. 243; no. 4889; pp. 398 - 400
• Main Authors: Sonsalla, Patricia K., Nicklas, William J., Heikkila, Richard E.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 20.01.1989; American Association for the Advancement of Science
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Amino acids; Amino Acids - physiology; Animals; Biochemistry; Biological and medical sciences; Brain damage; Corpus Striatum - drug effects; Dibenzocycloheptenes - pharmacology; Dizocilpine Maleate; Dopamine - metabolism; Dosage; Drugs; Excitatory amino acids; Intraperitoneal injections; Ketamine - pharmacology; Laboratory animals; Medical sciences; Methamphetamine; Methamphetamine - toxicity; Mice; Miscellaneous; N methyl D aspartate receptors; Neostriatum; Nervous system; Neurochemistry; Neuropharmacology; Neurotoxicity; Neurotoxins; Neurotransmitters; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Phencyclidine - pharmacology; Physiological aspects; Pyridines - toxicity; Substantia Nigra - drug effects; Tyrosine 3-Monooxygenase - metabolism; Amphetamine derivatives; Prevention; Nervous system diseases; Locus niger; Toxicity; Excitatory aminoacid; Dopaminergic neuron; Corpus striatum
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2563176

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.