Protective effect of riluzole on MPTP-induced depletion of dopamine and its metabolite content in mice

被引:6
作者
Araki, T [1 ]
Kumagai, T
Matsubara, M
Ido, T
Imai, Y
Itoyama, Y
机构
[1] Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Dept Clin Pharmacol & Therapeut, Sendai, Miyagi 9808578, Japan
[2] Tohoku Univ, Ctr Cyclotron & Radioisotope, Sendai, Miyagi 9808578, Japan
[3] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 9808578, Japan
关键词
MPTP; riluzole; pargyline; MK-801; dopamine; mice;
D O I
10.1023/A:1011111708901
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
The neuroprotective effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole), a Na+ channel blocker with antiglutamatergic activity, MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors and monoamine oxidase (MAO) inhibitor pargyline were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine and its metabolite 3, 4-dihydroxyphenyracetic acid (DOPAC) levels in mice. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at I-hr intervals and then the brains were analyzed at 1, 3 and 7 days after the treatments. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatments. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatments. Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine and DOPAC levels in the striatum. Pargyline also protected against MPTP-induced decrease in dopamine levels in the striatum. However, this drug showed no significant change in the striatal DOPAC levels. On the other hand, MK-801 failed to protect against MPTP-induced decrease in dopamine levels in the striatum. However, MK-801 reversed the MPTP-induced decrease in DOPAC levels. These results suggest that riluzole can protect against MPTP-induced striatal dopamine and DOPAC depletion in mice. This protective effect may be caused by inactivation of voltage-dependent Na+ channels by riluzole. Furthermore, the present study suggests that the activation of NMDA receptors does not mainly contribute to MPTP-induced neurodegeneration, whereas MAO, especially MAO type B(MAO-B) plays a crucial role in MPTP-induced degeneration of the nigrostriatal dopaminergic neuronal pathway.
引用
收藏
页码:193 / 201
页数:9
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