Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog

S. M N Efange, Deborah C Mash, F. Hefti, H. F. Kung, J. Billings

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The neurotoxic metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium, 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-[125I]iodobenzyl)-1,2,3,6-tetrahydropyridi e ([125I]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 [125I]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 [125I]MHTP, in vivo autoradiographic visualization of the rodent brain revealed selective accumulation of [125I]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 labelling of selected populations of catecholaminergic neurons.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalJournal of Neurochemistry
Volume53
Issue number2
StatePublished - Jan 1 1989

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Locus Coeruleus
Rodentia
Metabolites
Visualization
Radioactivity
Neurons
Intravenous Administration
Brain
Cells
1-Methyl-4-phenylpyridinium
Pargyline
Fibers
Dopaminergic Neurons
Monoamine Oxidase
Labeling
Rats
Dopamine
7-mercaptoheptanoylthreonine phosphate
Population

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Efange, S. M. N., Mash, D. C., Hefti, F., Kung, H. F., & Billings, J. (1989). Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog. Journal of Neurochemistry, 53(2), 459-464.

Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog. / Efange, S. M N; Mash, Deborah C; Hefti, F.; Kung, H. F.; Billings, J.

In: Journal of Neurochemistry, Vol. 53, No. 2, 01.01.1989, p. 459-464.

Research output: Contribution to journalArticle

Efange, SMN, Mash, DC, Hefti, F, Kung, HF & Billings, J 1989, 'Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog', Journal of Neurochemistry, vol. 53, no. 2, pp. 459-464.
Efange, S. M N ; Mash, Deborah C ; Hefti, F. ; Kung, H. F. ; Billings, J. / Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog. In: Journal of Neurochemistry. 1989 ; Vol. 53, No. 2. pp. 459-464.
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