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Selective Visualization of Rodent Locus Ceruleus by a Radiolabeled N ‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Analog
Author(s) -
Efange S. M. N.,
Mash D.,
Hefti F.,
Kung H. F.,
Billings J.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07356.x
Subject(s) - mptp , pargyline , catecholaminergic , locus ceruleus , monoamine oxidase , dopaminergic , dopamine , metabolite , chemistry , in vivo , catecholaminergic cell groups , neuromelanin , pharmacology , locus coeruleus , neurotoxin , medicine , endocrinology , substantia nigra , biology , biochemistry , central nervous system , enzyme , microbiology and biotechnology
The neurotoxic metabolite of N ‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), 1 ‐methyl‐4‐phenylpyr‐idinium, selectively accumulates in dopaminergic neurons via the dopamine reuptake system. Consequently, nontoxic radiolabeled MPTP analogs may be potentially useful for visualizing catecholaminergic neurons in vivo. N ‐Methyl‐4‐(4 ‐ hydroxy ‐ 3 ‐ [ l25 I]iodobenzyl) ‐1,2,3,6 ‐ tetrahydropyridine ([ l25 I]MHTP), an analog of the nontoxic N ‐methyl‐4‐benzyl‐1,2,3,6‐tetrahydropyridine, has been studied in rats and mice. After intravenous administration of [ 125 I]MHTP to rodents, the initial accumulation of radioactivity within the brain was found to be comparable to that of radiolabeled MPTP. Following intravenous administration of [ 125 I]MHTP, in vivo autoradiographic visualization of the rodent brain revealed selective accumulation of [ I25 I]MHTP‐derived radioactivity within the locus ceruleus; there was no accumulation of the radiotracer within dopaminergic fibers and cell bodies. The accumulation of radioactivity within the locus ceruleus was blocked by pretreatment with pargyline, a result suggesting that an MHTP metabolite formed by monoamine oxidase was responsible for the localization of the radiotracer within this structure. The anatomical distribution of the radiolabel demonstrates selective accumulation of this metabolite within noradrenergic cell bodies and those fibers making up the locus ceruleus. These findings further suggest that nontoxic metabolites of MPTP may become useful for in vivo labeling of selected populations of catecholaminergic neurons.