title: Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine.
abstract: Several lines of evidence suggest that oxidative stress might contribute to neurotoxicity in the dopaminergic nerve terminals after administration of methamphetamine (MAP). We undertook the present study to determine whether intravenous administration of N-acetyl-L-cysteine (NAC), a potent antioxidant drug, could attenuate the reduction of dopamine transporter (DAT) in the striatum of monkey brain after administration of MAP. Positron emission tomography studies demonstrated that repeated administration of MAP (2 mg/kg as a salt, four times at 2-h intervals) significantly decreased the accumulation of radioactivity in the striatum after intravenous administration of [11C]beta-CFT. In contrast, the binding of [11C]SCH 23390 to dopamine D1 receptors in the monkey striatum was not altered after the administration of MAP. A bolus injection of NAC (150 mg/kg, i.v.) 30 min before MAP administration and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h significantly attenuated the reduction of DAT in the monkey striatum 3 weeks after the administration of MAP. These results suggest that NAC could attenuate the reduction of DAT in the monkey striatum after repeated administration of MAP. Therefore, it is likely that NAC would be a suitable drug for treatment of neurotoxicity in dopaminergic nerve terminals related to chronic use of MAP in humans.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. hashimoto@faculty.chiba-u.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumoto
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kakiuchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008694:Methamphetamine / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D008694:Methamphetamine; D000111:Acetylcysteine