Pargyline increases 6-hydroxydopamine levels in the neostriatum of methamphetamine-treated rats.
Neostriatal 6-hydroxydopamine (6-OHDA) was detected in 6 of 13 rats pretreated 2 or 4 hr earlier with methamphetamine (MA; 100 mg/kg, SC) and pargyline (25 mg/kg, IP, 30 min before MA injection). Neostriatal 6-OHDA was detected in 2 of 16 rats treated 2 or 4 hr earlier with MA. These results suggest that pargyline pretreatment may enhance formation of 6-OHDA from endogenous stores of dopamine (DA) following MA administration. Alternatively, these results suggest that pargyline pretreatment may protect endogenously formed 6-OHDA from oxidative deamination by monoamine oxidase. Enhancement of MA-induced neostriatal 6-OHDA levels may be the mechanism by which pargyline enhances the long-term neurotoxic effects of MA upon dopaminergic nerve terminals. These observations support the hypothesis that MA toxicity to DA-containing fibers is caused by the conversion of released DA into 6-OHDA.
Marek
G J
GJ
University of Chicago, Department of Pharmacological Science, IL 60637.
Vosmer
G
G
Seiden
L S
LS
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D006892:Hydroxydopamines / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D016627:Oxidopamine; D010293:Pargyline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006892:Hydroxydopamines; D008694:Methamphetamine; D016627:Oxidopamine; D010293:Pargyline