Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated common marmoset
| Autor: | R. K. B. Pearce, B.C. Tel, L. Chancharme, L. A. Smith, Bai-Yun Zeng, G. Moachon, Peter Jenner |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Tyrosine 3-Monooxygenase Dopamine Movement animal diseases Nigrostriatal pathway Modafinil Substantia nigra Pharmacology Tritium Neuroprotection chemistry.chemical_compound Dopamine Uptake Inhibitors biology.animal mental disorders medicine Animals Neurotoxin Benzhydryl Compounds Neurons Behavior Animal biology business.industry General Neuroscience MPTP MPTP Poisoning Marmoset Callithrix Mazindol nervous system diseases Substantia Nigra Neuroprotective Agents medicine.anatomical_structure nervous system chemistry Anesthesia Toxicity Autoradiography Female business medicine.drug |
| Zdroj: | Experimental Brain Research. 133:178-188 |
| ISSN: | 1432-1106 0014-4819 |
| DOI: | 10.1007/s002210000370 |
| Popis: | The psychostimulant drug, modafinil, protects rodents against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, striatal ischemia and partial transection of the nigro-striatal pathway. We now report on the ability of modafinil to reverse motor disability in MPTP-treated common marmosets and to prevent MPTP-induced nigral cell death in this species. In the initial experiments, adult common marmosets were treated with MPTP to produce stable motor deficits. The subsequent administration of modafinil (10, 30 or 100 mg/kg/day, p.o.) produced a dose-dependent reversal of motor disability. In a subsequent experiment, normal common marmosets were concurrently treated with 10, 30 or 100 mg/kg of modafinil once daily by gavage during acute MPTP administration (daily for 5 days), continuing for 2 weeks after the last dose of MPTP. Modafinil dose-dependently prevented the decline in motor activity normally produced by MPTP treatment. MPTP treatment caused a 76% loss of nigral tyrosine-hydroxylase-immunoreactive cells in placebo-treated animals, and this was dose-dependently prevented by modafinil. At the highest dose (100 mg/kg/day) of modafinil, there was no significant loss of tyrosine-hydroxylase-immunoreactive cells in the substantia nigra compared with normal animals. MPTP treatment also reduced striatal dopamine uptake sites by 95%, as measured by specific [3H]-mazindol binding, compared with normal controls. Modafinil treatment dose-dependently reduced the loss of specific [3H]-mazindol binding. Behavioural and morphological evidence in the present study indicate a potential antiparkinsonian and neuroprotective role for modafinil, which may form a new pharmacological approach to the treatment of Parkinson's disease. |
| Databáze: | OpenAIRE |
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