Attenuation of paraquat-induced dopaminergic toxicity on the substantia nigra by (-)-deprenyl in vivo

(-)-Deprenyl (DEP) had been shown to slow of progression of Parkinson's dis ease (PD). The present study sought to determine whether DEP would attenuat e the nigrostriatal system damage induced by intranigral administration of the herbicide paraquat (PQ) as a model of parkinsonism in vivo. Neurochemic al and behavioral observations of Wistar rats were the focus of our study. In the neurochemical observation, the PQ injected in the rats caused dose-d ependent depletion of dopamine (DA) in the ipsilateral striata. The coadmin istration of DEP with PQ partially increased the striatal DA level. The pre diction of the striatal DA levels was calculated by regression coefficients obtained from multiple linear regression (r(2) = 0.82): DA level (% of con trol) = 103.34 - 9.58 PQ (nmol) + 0.79 DEP (nmol). It was demonstrated that the high dose of 20 nmol DEP could significant attenuate the PQ (5 nmol)-e licited dopaminergic toxicity (p < 0.05). In the behavioral observation, th e intranigral injection of PQ into the rats caused a rotation behavior cont ralateral to the lesioned side in response to apomorphine administration (0 .5 mg/kg, sc). This apomorphine-induced rotational behavior could also be a ttenuated significantly by coadministration of DEP (20 nmol) and PQ (5 nmol ) compared with PQ-treated (5 nmol) animals (p < 0.05). The above observati ons indicate that DEP could provide a protective effect on the moderate inj ury elicited by PQ toxicity of the nigro-strital dopaminergic system. DEP m ight be a useful therapeutic agent in treating patients with early-stage PD . (C) 2001 Academic Press.