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.