Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine.
Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 +/- 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 +/- 4.3, 27.3 +/- 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.
Department of Environmental and Occupational Health, National Health Research Institutes, Kaoshung, Taiwan.
P C
PC
Liao
Y M
YM
Kuo
Y C
YC
Chang
C
C
Lin
C F G
CF
Cherng
L
L
Yu
D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016627:Oxidopamine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology*; D011748:Pyrogallol / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013565:Sympatholytics / Q000378:metabolism
D065098:Catechol O-Methyltransferase Inhibitors; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D013565:Sympatholytics; D011748:Pyrogallol; D008694:Methamphetamine; D016627:Oxidopamine; D010293:Pargyline