Influence of selective inhibition of monoamine oxidase A or B on striatal metabolism of L-DOPA in hemiparkinsonian rats.

Abstract:

:The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) was studied in halothane-anesthetized rats 3 weeks after unilateral 6-hydroxydopamine lesion of the substantia nigra. Implantation of bilateral microdialysis probes allowed simultaneous quantitation of metabolite production on lesioned and control sides. The DOPA was administered as a 15-min bolus of 1 mM solution in the striatal microdialysate. Rats were pretreated with the selective MAO-A inhibitor clorgyline, or the selective MAO-B inhibitors deprenyl or TVP-101 [2,3-dihydro-N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride]. Intrastriatal infusion of DOPA caused an increased efflux of DA, DOPAC, and HVA, which was greater on the intact side. Clorgyline, but not deprenyl or TVP-101, increased post-DOPA DA efflux on both intact and lesioned sides. Clorgyline also caused a marked suppression of post-DOPA DOPAC and HVA effluxes, whereas only mild effects were produced by the MAO-B inhibitors. There was no evidence for a differential effect of MAO-B inhibition on efflux of DA or metabolites in the lesioned as compared with the control striatum. The results indicate a major role for MAO-A in DA metabolism both intra- and extraneuronally in the rat striatum.

journal_name

J Neurochem

authors

Finberg JP,Wang J,Goldstein DS,Kopin IJ,Bankiewicz KS

doi

10.1046/j.1471-4159.1995.65031213.x

subject

Has Abstract

pub_date

1995-09-01 00:00:00

pages

1213-20

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

65

pub_type

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