Differential effects of L-deprenyl on MPP+- and MPTP-induced dopamine overflow in microdialysates of striatum and nucleus accumbens

Citation
Wr. Wu et al., Differential effects of L-deprenyl on MPP+- and MPTP-induced dopamine overflow in microdialysates of striatum and nucleus accumbens, LIFE SCI, 67(3), 2000, pp. 241-250
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
0024-3205 → ACNP
Volume
67
Issue
3
Year of publication
2000
Pages
241 - 250
Database
ISI
SICI code
0024-3205(20000608)67:3<241:DEOLOM>2.0.ZU;2-C
Abstract
The present studies investigated the effects of L-deprenyl, 1-methyl-4-phen ylpyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (M PTP) on the efflux of dopamine and its metabolites in microdialysates of st riatum and nucleus accumbens in rats. L-Deprenyl or L-amphetamine perfusion into striatum had no effects on basal dopamine efflux, though L-deprenyl r educed the basal efflux of dihydroxyphenylacetic acid and homovanillic acid . MPP+ or MPTP perfusion into striatum significantly increased the dopamine efflux, and the action of MPTP was more potent than that of MPP+. Pretreat ment with L-deprenyl antagonized the actions of MPP+ and MPTP. The striatal dopamine efflux of rats was gradually restored by itself after the overflo w caused by 2-h perfusion of the dopaminergic neurotoxins, while L-deprenyl could not accelerate the recovery. Perfusion with L-deprenyl or L-amphetam ine, but not pargyline, into nucleus accumbens increased the dopamine efflu x in a dose-dependent fashion, which could be antagonized by haloperidol pr etreatment, MPP+ or MPTP perfusion into nucleus accumbens also increased th e dopamine efflux, and the action of MPTP was also more potent than that of MPP+. Pretreatment with L-deprenyl could not antagonize the actions of MPP + and MPTP. These findings suggest that L-deprenyl, MPP+ and MPTP induce di fferential effects on nigrostriatal and mesolimbic dopaminergic pathways in vivo. L-Deprenyl has neuroprotective rather than neurorestorative action a gainst MPP+- and MPTP-induced dopamine overflow from striatum. Further, L-d eprenyl-induced dopamine overflow from nucleus accumbens may explain the am phetamine-like reinforcing property of L-deprenyl. (C) 2000 Elsevier Scienc e Inc. All rights reserved.