Summary
Protective effects of NMDA antagonists on dopaminergic and serotonergic neurotoxicity produced by methamphetamine (MA) were examined. Four injections of MA (7.5 mg/kg, s.c., at 2 h intervals) caused significant decrements (40–60% of control values) in levels of dopamine (DA) and its metabolites in the rat striatum and levels of serotonin (5-HT) and its metabolite in the medial prefrontal cortex, nucleus accumbens, striatum, anterior hypothalamus, amygdala and hippocampus. These decreases in DA, 5-HT and their metabolites were prevented by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, or D-CPP-ene (SDZ EAA 494), a competitive NMDA antagonist. The results suggest that NMDA receptors play a role for MA-induced serotonergic damage in various brain regions as well as dopaminergic damage in the striatum.
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References
Bakhit C, Morgan ME, Peat MA, Gibb JW (1981) Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain. Neuropharmacology 20: 1135–1140
Bowery NG, Wong EHF, Hudson AL (1988) Quantitative autoradiography of [3 H]-MK-801 binding sites in mammalian brain. Br J Pharmacol 93: 944–954
Buening MK, Gibb JW (1974) Influence of methamphetamine and neuroleptic drugs on tyrosine hydroxylase activity. Eur J Pharmacol 26: 30–34
Clow DW, Jhamanadas K (1989) Characterization of L-glutamate action on the release of endogenous dopamine from the rat caudate-putamen. J Pharmacol Exp Ther 248: 722–728
Fagg GE, Foster AC (1983) Amino acid neurotransmitters and their pathways in the mammalian central nervous system. Neuroscience 9: 701–719
Green AR, De Souza RJ, Williams JL, Murray TK, Cross AJ (1992) The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole. Neuropharmacology 31: 315–321
Hotchkiss AJ, Gibb JW (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
Johnson M, Stone DM, Hanson GR, Gibb JW (1987) Role of the dopaminergic nigrostriatal pathway in methamphetamine-induced depression of the neostriatal serotonergic system. Eur J Pharmacol 135: 231–234
Johnson M, Hanson GR, Gibb JW (1989) Effect of MK-801 on the decrease in tryptophan hydroxylase induced by methamphetamine and its methylenedioxy analog. Eur J Pharmacol 165: 315–318
Jones SM, Snell LD, Johnson KM (1987) Inhibition by phencyclidine of excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens. Neuropharmacology 26: 173–179
Krebs MO, Desce JM, Kernel ML, Gauchy C, Godeheu G, Cheramy A, Glowinski J (1991) Glutamatergic control of dopamine release in the rat striatum: evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals. J Neurochem 56: 81–85
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Monaghan DT, Cotman CW (1985) Distribution of N-methyl-D-aspartate-sensitive L-[3 H] glutamate-binding sites in rat brain. J Neurosci 5: 2909–2919
Morgan ME, Gibb JW (1980) Short-term and long-term effects of methamphetamine on biogenic amine metabolism in extra-striatal dopaminergic nuclei. Neuropharmacology 19: 989–995
Ohmori T, Koyama T, Yamashita I (1991) Effects of N-methyl-D-aspartate and related agents on dopamine release from superfused slices of rat striatum. In: Kameyama T, Nabeshima T, Domino EF (eds) NMDA receptor related agents: biochemistry, pharmacology, and behavior. NPP Books, Ann Arbor MI, pp 129–139
Ohmori T, Nakamura F, Koyama T, Yamashita I (1992) Amygdala kinding does not alter the N-methyl-D-aspartate receptor-channel complex which modulates dopamine release in the rat striatum and amygdala. Brain Res 587: 257–262
Palkovits M, Brounstein MJ (1988) Maps and guide to microdissection of the rat brain. Elsevier, New York
Ricaurte GA, Schuster CR, Seiden LS (1980) Long-term effects of repeated methamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional sutdy. Brain Res 193: 153–163
Schmidt CJ, Ritter JK, Sonsalla PK, Hanson GR, Gibb JW (1985) Role of dopamine in the neurotoxic effects of methamphetamine. J Pharmacol Exp Ther 233: 539–544
Seiden LS, Fischman MW, Schuster CR (1975/76) Long-term methamphetamine induced changes in brain catecholamines in tolerant rhesus monkeys. Drug Alcohol Depend 1: 215–219
Snell LD, Johnson KM (1986) Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs. J Pharmacol Exp Ther 238: 938–946
Sonsalla PK, Gibb JW, Hanson GR (1986) Roles of D 1 and D 2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems. J Pharmacol Exp Ther 238: 932–937
Sonsalla PK, Nicklas WJ, Heikkila RE (1989) Role for excitatory amino acids in meth-amphetamine-induced nigrostriatal dopaminergic toxicity. Science 243: 398–400
Sonsalla PK, Riordan DE, Heikkila RE (1991) Competitive and noncompetitive antagonists at N-methyl-D-aspartate receptors protect against methamphetamine-induced dopaminergic damage in mice. J Pharmacol Exp Ther 256: 506–512
Weihmuller FB, O'Dell SJ, Marshall JF (1992) MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow. Synapse 11: 155–163
Yamamoto BK, Nash JF (1991) Methamphetamine neurotoxicity and striatal glutamate release. Soc Neurosci Abstr 17: 1429
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Ohmori, T., Koyama, T., Muraki, A. et al. Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity produced by methamphetamine in various brain regions. J. Neural Transmission 92, 97–106 (1993). https://doi.org/10.1007/BF01244869
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DOI: https://doi.org/10.1007/BF01244869