Depletion of striatal dopamine by the N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Abstract:

:The N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the major metabolite found in vivo and excreted in urine after the parenteral administration of the neurotoxicant, MPTP. In mice (C57BL/6), stereotaxic injection of MPTP N-oxide (15 micrograms) into the neostriatum produced dopamine (DA) depletion similar to that caused by MPTP. The DA depleting effect of MPTP N-oxide was a direct action, whereas the action of MPTP was mediated by the generation of oxidative metabolites. In the mouse striatal synaptosomal preparation, MPTP, MPP+ and MPTP N-oxide all competed with [3H]DA at its uptake site. In addition, MPP+ and MPTP N-oxide promoted [3H]DA release. In contrast to MPTP and MPDP+, MPTP N-oxide did not alter the electrophysiologically recorded field potential in nigro-striatal slices. These observations suggest that MPTP N-oxide can directly cause the chemical depletion of striatal DA without modifying the characteristics of cortico-striate synaptic transmission.

journal_name

Neurotoxicology

journal_title

Neurotoxicology

authors

Lau YS,Fung YK,Trobough KL,Cashman JR,Wilson JA

subject

Has Abstract

pub_date

1991-07-01 00:00:00

pages

189-99

issue

2

eissn

0161-813X

issn

1872-9711

journal_volume

12

pub_type

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