Intrastriatal microinjection of sodium nitroprusside induces cell death and reduces binding of dopaminergic receptors

Rat striatum was microinjected with 50 nmol sodium nitroprusside (SNP) and neural cell death as well as the binding of dopaminergic receptors were followed for 24 h after the infusion using TTC staining, cresyl violet staining, and quantitative autoradiography. Striatal cell death was observed 3 h after the infusion of SNP. A widespread area of cell death, including part of the cerebral cortex, was seen at 24 h after the infusion. A decrease of more than 80% in dopamine D₁ receptor binding was seen in rat brain slices prepared 2 h after the infusion of SNP, whereas only a slight decrease in dopamine D₂ receptor binding and almost no changes in dopamine transporter binding were observed. One day after the infusion, less than 10% of the binding of all three types of dopaminergic receptors remained in a widespread area in the infused side of the striatum and part of the cerebral cortex. Microinjection of either NOC-18 (50 nmol), another type of NO donor, or sodium cyanide (50 nmol) did not caused cell death. In addition, microinjection of FeCl₂ (50 nmol) into the striatum caused cell death and reduction in dopamine D₁ receptor binding. These results suggest that iron-related radical reactions, but not NO itself, might have important roles on SNP-caused cell death. The current receptor binding study also indicated that dopamine D₁ receptor binding is the most sensitive indicator for detection of cell death or cell damage induced by radical reactions in the rat striatum.