Hydroxyl radical formation following methamphetamine administration to rats.
Administration of neurotoxic doses of methamphetamine (8 mg/kg, intraperitoneally x 4 times, at 2 hr intervals) caused a significant decrease in dopamine and 3,4-dihydroxyphenylacetic acid and an increase in 3-methoxytyramine levels in the striatum along with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in the striatum and hippocampus. In addition, the methamphetamine treatment caused an increase in rat rectal temperature. Intraventricular injection of salicylate 105 min. after the last injection of methamphetamine produced an increase in 2,3- and 2,5-dihydroxybenzoic acid in the striatum and hippocampus. Moreover, the ratio of 2,3-dihydroxybenzoic acid to salicylate was significantly increased in the striatum, but not in the hippocampus. These results indicate that the hydroxyl radical may play an important role in methamphetamine-induced neurotoxicity in rat striatum and that its formation may be the result of methamphetamine-induced release of dopamine.
Kita
T
T
Department of Pharmacology, Nara Medical University, Kashihara, Japan. tkita@nmu-gw.cc.naramed-u.ac.jp
Takahashi
M
M
Kubo
K
K
Wagner
G C
GC
Nakashima
T
T
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005841:Gentisates; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D005841:Gentisates; D062385:Hydroxybenzoates; D012459:Salicylates; D012701:Serotonin; D017665:Hydroxyl Radical; D008694:Methamphetamine; C009135:2,3-dihydroxybenzoic acid; C001746:3-methoxytyramine; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine