The effects of monoamine oxidase inhibition and dopamine uptake blockade on MPTP-induced increase of 2-[3H]deoxyglucose uptake in specific mesencephalic catecholaminergic nuclei.
Intraperitoneal injection in C57 black mice of 30 or 7.5 mg/kg MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) followed 1-2 h later by 0.5 mCi/100 g 2-[3H]deoxyglucose (2-DG) produces an intense increase of 2-DG uptake in the dopaminergic zona compacta (ZC) of the substantia nigra and the adjacent ventral tegmental area (VTA) as seen in autoradiographs. Anesthetized animals also exhibit this reaction. Clorgyline (10 mg/kg), a monoamine oxidase (MAO)-A inhibitor, 30 min before MPTP does not block this reaction. Deprenyl (10 mg/kg), an MAO-B inhibitor, blocks increased 2-DG uptake in ZC and VTA if injected 30 min or 12 h before 7.5 mg/kg MPTP, but has no effect if injected 12 h before 30 mg/kg MPTP. Mazindol (10 mg/kg), a dopamine uptake blocker, is effective in blocking the action of 7.5 mg/kg MPTP, but ineffective against 30 mg/kg MPTP. Heavier doses of MPTP can, in some instances, overcome the actions of MAO inhibitors or dopamine uptake blockers in preventing the increased 2-DG uptake elicited by MPTP. But, essentially, the intensely increased glucose metabolism acutely induced in specific catecholaminergic neurons appears to be another significant pathological feature of the dopaminergic neurotoxicity caused by MPTP which can be prevented by MAO inhibition or dopamine uptake blockade.
Hess
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Department of Anatomy, Robert Wood Johnson Medical School, University of Medicine and Dentistry, Piscataway, NJ 08854.
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004298:Dopamine / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D020267:MPTP Poisoning; D008454:Mazindol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism*
D003837:Deoxy Sugars; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D012642:Selegiline; D003847:Deoxyglucose; D008454:Mazindol; D003010:Clorgyline; D004298:Dopamine