title: A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.
abstract: The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion. These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.
authors.affiliation: Department of Physiology, School of Medicine, Malaga, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Aguirre
authors.forename: A
authors.initials: A
authors.lastname: Cintra
authors.forename: J
authors.initials: J
authors.lastname: Hillion
authors.forename: J A
authors.initials: JA
authors.lastname: Narváez
authors.forename: A
authors.initials: A
authors.lastname: Jansson
authors.forename: T
authors.initials: T
authors.lastname: Antonelli
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
authors.forename: F A
authors.initials: FA
authors.lastname: Rambert
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000077408:Modafinil; D004298:Dopamine