DOPAMINERGIC MODULATION OF EARLY SIGNS OF EXCITOTOXICITY IN VISUALIZED RAT NEOSTRIATAL NEURONS

Cell swelling induced by activation of excitatory amino acid receptors is presumably the first step in a toxic cascade that may ultimately l ead to cell death. Previously we showed that bath application of N-met hyl-D-aspartate (NMDA) or kainate (KA) produces swelling of neostriata l cells. The present experiments examined modulation of NMDA and KA-in duced cell swelling by dopamine (DA) and its receptor agonists. Nomars ki optics and infra-red videomicroscopy were utilized to visualize neo striatal medium-sized neurons in thick slices from rat pups (12-18 pos tnatal days), increase in somatic cross-sectional area served as the i ndicator of swelling induced by bath application of glutamate receptor agonists. NMDA induced cell swelling in a dose-dependent manner. Acti vation of DA receptors in the absence of NMDA did not produce swelling . DA and the D-1 receptor agonist SKF 38393, increased the magnitude o f swelling produced by NMDA. This effect was reduced in the presence o f the D-1 receptor antagonist, SCH 23390. In contrast, activation of D -2 receptors by quinpirole decreased the magnitude of NMDA-induced cel l swelling. DA slightly attenuated cell swelling induced by activation of KA receptors. Quinpirole produced a significant concentration-depe ndent reduction in KA-induced swelling while SKF38393 increased KA-ind uced swelling, but only at a low concentration of KA. Together, these results provide additional support for the hypothesis that the directi on of DA modulation depends on the glutamate receptor subtype, as well as the DA receptor subtype activated. One possible consequence of the se observations is that endogenous DA may be an important contributing factor in the mechanisms of cell death in Huntington's disease.