Differential effects of L-deprenyl on MPP+- and MPTP-induced dopamine overflow in microdialysates of striatum and nucleus accumbens.
The present studies investigated the effects of L-deprenyl, 1-methyl-4-phenylpyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the efflux of dopamine and its metabolites in microdialysates of striatum and nucleus accumbens in rats. L-Deprenyl or L-amphetamine perfusion into striatum had no effects on basal dopamine efflux, though L-deprenyl reduced 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+. Pretreatment with L-deprenyl antagonized the actions of MPP+ and MPTP. The striatal dopamine efflux of rats was gradually restored by itself after the overflow caused by 2-h perfusion of the dopaminergic neurotoxins, while L-deprenyl could not accelerate the recovery. Perfusion with L-deprenyl or L-amphetamine, but not pargyline, into nucleus accumbens increased the dopamine efflux in a dose-dependent fashion, which could be antagonized by haloperidol pretreatment. MPP+ or MPTP perfusion into nucleus accumbens also increased the 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 differential effects on nigrostriatal and mesolimbic dopaminergic pathways in vivo. L-Deprenyl has neuroprotective rather than neurorestorative action against MPP+- and MPTP-induced dopamine overflow from striatum. Further, L-deprenyl-induced dopamine overflow from nucleus accumbens may explain the amphetamine-like reinforcing property of L-deprenyl.
Wu
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Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. wrwu@vetmed.wsu.edu
Zhu
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Zhu
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine