DIFFERENTIAL NEUROTOXICITY INDUCED BY L-DOPA AND DOPAMINE IN CULTUREDSTRIATAL NEURONS

The neurotoxicity of L-DOPA and dopamine (DA) on striatal neurons was examined by using primary cultures of rat striatum. Exposure to L-DOPA and DA at concentrations of 30-300 mu M induced dose-dependent cell d eath in both younger cultures (3 days in culture, 3 DIC) and elder cul tures (10 days in culture, 10 DIC). The cytotoxicity of L-DOPA and DA was also dependent on the exposure time (6-24 h). Ascorbic acid (200 m u M) inhibited both L-DOPA- and DA-induced cytotoxicity in 3 DIC cultu res, whereas it provided significant protection against DA- but not L- DOPA-induced cytotoxicity in 10 DIC cultures. The L-DOPA cytotoxicity in 10 DIC cultures was prevented by a non-NMDA receptor antagonist, 6- cyano-7-nitroquinoxaline-2,3-dione (CNQX), and by an NMDA receptor ant agonist, MK-801. Neither antagonist prevented DA cytotoxicity. D-DOPA did not affect the viability of 10 DIC cultures, though it elicited ma rked toxicity in 3 DIC cultures. These results suggest that there are two components in the mechanisms that mediate the L-DOPA neurotoxicity on striatal neurons: one is autoxidation-relevant and the other is au toxidation-irrelevant. With respect to the latter, glutamate receptor stimulation may be involved. In contrast, autoxidation plays an import ant role in DA neurotoxicity.