Methamphetamine enhances 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in the rat striatum.
We determined the methamphetamine (MA), a potent dopamine (DA) releaser, enhances 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (&z.rad;OH) generation in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the generation of .OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. After administration of MA (5 mg/kg i.v., every 2 h, four times), MA drastically increased DA release and the &z.rad;OH formation. When iron (II) was administered to the MA-treated animals, a marked elevation of DHBA was observed, compared with MPP(+)-only treated animals, that showed a positive linear correlation between DA and .OH formation trapped as DHBA (R(2)=0.985) in the dialysate. These results suggest that MA enhances the &z.rad;OH products of efflux/oxidation due to MPP(+).
Obata
T
T
Department of Pharmacology, Oita Medical University, Hasama-machi, 879-5593, Oita, Japan. tobata@oita-med.ac.jp
Yamanaka
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004563:Electrochemistry; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
D018765:Dopamine Uptake Inhibitors; D017665:Hydroxyl Radical; D008694:Methamphetamine; D015655:1-Methyl-4-phenylpyridinium