Dopamine-induced protection of striatal neurons against kainate receptor-mediated glutamate cytotoxicity in vitro

Abstract

The effects of dopamine on glutamate-induced cytotoxicity were examined using the primary cultures of rat striatal neurons. Cell viability was significantly reduced by exposure of cultures to glutamate or kainate for 24 h. In contrast, similar application of N- methyl- d-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) did not induce cytotoxicity. Kainate-induced cytotoxicity was significantly inhibited by kynuurenate but not by MK-801. Dopamine at concentrations of 1–100 μM dose-dependently reduced kainate-induced cytotoxicity. Forskolin also significantly reduced kainate cytotoxicity. The neuroprotective effect of dopamine was antagonized by SCH 23390, a D 1 receptor antagonist, but not by domperidone, a D 2 not by quinpiirole, a D 2 receptor agonist. The patch study revealed that the same striatal neurons responded to both kainate and NMDA. During voltage clamp recording, neither kainate-induced currents nor NMDA-induced current were affected by dopamine. Moreover, dopamine did not affect glutamate- or kainate-induced Ca 2+ influx measured with fura-2. These findings indicate that dopamine prevents kainate receptor-mediated cytotoxicity without affecting the kainate receptor activities and intracellular Ca 2+ movement. Dopamine-induced neuroprotection may be mediated by an increased intracellular cAMP formed following activation of D 1 receptors.