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 disease (PD). The present study sought to determine whether DEP would attenuate the nigrostriatal system damage induced by intranigral administration of the herbicide paraquat (PQ) as a model of parkinsonism in vivo. Neurochemical and behavioral observations of Wistar rats were the focus of our study. In the neurochemical observation, the PQ injected in the rats caused dose-dependent depletion of dopamine (DA) in the ipsilateral striata. The coadministration of DEP with PQ partially increased the striatal DA level. The prediction of the striatal DA levels was calculated by regression coefficients obtained from multiple linear regression (r(2) = 0.82): DA level (% of control) = 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)-elicited dopaminergic toxicity (p < 0.05). In the behavioral observation, the intranigral injection of PQ into the rats caused a rotation behavior contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc). This apomorphine-induced rotational behavior could also be attenuated significantly by coadministration of DEP (20 nmol) and PQ (5 nmol) compared with PQ-treated (5 nmol) animals (p < 0.05). The above observations indicate that DEP could provide a protective effect on the moderate injury elicited by PQ toxicity of the nigrostriatal dopaminergic system. DEP might be a useful therapeutic agent in treating patients with early-stage PD.
Departments of Pharmacology and Neurology, College of Medicine National Taiwan University, Taipei, Taiwan. hhliou@ha.ntu.edu.tw
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Chen
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D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
D018491:Dopamine Agonists; D006540:Herbicides; D018696:Neuroprotective Agents; D012642:Selegiline; D001058:Apomorphine; D010269:Paraquat; D004298:Dopamine