Ouabain-induced increase in dopamine release from mouse striatal slices isantagonized by riluzole

We have examined the effects of riluzole, a neuroprotective drug which stab ilizes voltage-dependent sodium channels in their inactivated state and inh ibits the release of glutamate in-vivo and in-vitro, on the release of newl y taken up [H-3]dopamine induced by ouabain, a potent and selective inhibit or of Na+/K+-ATPase in mouse striatal slices in-vitro. Riluzole potently (IC50 (concentration resulting in 50% inhibition) = 0.9 /- 0.3 mu M) and dose-dependently antagonized ouabain-stimulated [3H]dopami ne release, the effect being observed at low concentrations. Tetrodotoxin ( 1 mu M) and nomifensine (10 mu M) also abolished ouabain-induced [H-3]dopam ine release. Blockade of glutamate receptors with dizocilpine (1 mu M) and 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione (YM90K; 10 mu M), alone or in combination, was without effect. Incubation of striatal slices with 50 mu M La3+, which blocks voltage-dependent calcium channels, did not inhibit [H-3]dopamine release induced by ouabain. The potent effects of riluzole observed in this model are probably related to its ability to block voltage-dependent sodium channels. The consequences of this activity are critically discussed in relation to the protective ac tion of riluzole previously reported in various models of Parkinson's disea se and other neurodegenerative disorders.