title: Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity produced by methamphetamine in various brain regions.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohmori
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.forename: A
authors.initials: A
authors.lastname: Muraki
authors.forename: I
authors.initials: I
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
chemical_list: D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D004298:Dopamine