Positive and negative modulation by AMPA- and kainate-receptors of striatal kainate injection-induced neuronal loss in rat forebrain.

We investigated the roles of ionotropic glutamate receptor subtypes in mediating striatal kainate injection-induced neuronal loss in rat forebrain, using subtype-specific antagonists and histochemical staining. Our study demonstrates that kainate injected unilaterally into the striatum induces a massive neuronal loss in the rat ipsilateral forebrain through activation of kainate receptors and, to a limited extent, a consequent involvement of M-methyl-D-aspartate (NMDA) receptors, whereas activation of alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors shows a neuroprotective effect. These and previous results suggest that three subtypes of ionotropic glutamate receptors play differential roles in mediating excitatory amino acid (EAA)-induced neurodegeneration.