Abstract
The vigilance promoting drug Modafinil has been demonstrated to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity (40 mg/kg sc) in the nigrostriatal dopamine (DA) system of the black mouse.16,29 A single dose of Modafinil (30 mg/kg ip, at different time intervals before and after MPTP) significantly counteracted the MPTP-induced depletion of striatal dopamine (DA) as analyzed 14 days later. A similar treatment protocol showed that Modafinil significantly counteracted the paradoxical MPTP-induced increase in locomotion and motility. Chronic administration of Modafinil (30 mg/kg ip daily for 14 days) led to a more pronounced counteraction of the MPTP-induced decrease in striatal DA and also attenuated the MPTP-induced increase in DA turnover. After a similar chronic treatment with Modafinil (10–100 mg/kg) the disappearance of tyrosine hydroxylase immunoreactive neurons in substantia nigra appeared to be dose-dependently counteracted.
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