Role of corticostriatal and nigrostriatal inputs in malonate-induced striatal toxicity.

The striatal neuronal loss evident following cellular metabolic compromise may be dependent upon the presence of glutamate and dopamine within the striatum. In order to investigate the relative roles of corticostriatal and nigrostriatal projections in malonate-induced neuronal loss, the extent of toxicity was quantified in animals with cortical lesions to deplete the striatum of glutamate, nigrostriatal lesions to deplete the striatum of dopamine, or both. We found that malonate-induced striatal toxicity was significantly reduced following lesions of either the glutamatergic or dopaminergic afferents to the striatum. The extent of attenuation following the loss of both inputs within the same animal was similar to that seen following lesions of either alone. These data suggest that malonate-induced toxicity in the striatum depends upon the integrity of interactive influences from both glutamatergic and dopaminergic afferents.