Local infusion of the (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione does not block d 1 dopamine receptor-mediated increases in immediate early gene expression in the dopamine-depleted striatum

Abstract

Administration of selective agonists of D, dopamine receptors increases immediate early gene expression in striatal neurons, a response which is particularly robust in the dopamine-depleted striatum. Although interactions between dopamine and glutamate receptor-mediated responses in striatal neurons have been demonstrated in a number of experimental paradigms, our previous findings indicate that N-methyl- d-aspartate antagonists do not block D 1 receptor-mediated induction of immediate early genes in the dopamine-depleted striatum. In the present study, we therefore examined interactions between D 1 dopamine receptors and the (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate subtypes of glutamate receptor by determining whether striatal infusion of the (±)-a-amino-3-hydroxy-5-5-methylisoxazole-4-propionate/kainate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione would block D 1 receptor-mediated induction of the immediate early genes c- fos and zif268 in the dopamine-depleted striatum. Striatal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (1 mM) completely blocked (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate-induced c- fos and zif268 expression. However, 6-cyano-7-nitroquinoxaline-2,3-dione (1 μM−1 mM) did not significantly affect induction of c- fos and zif268 by D 1 receptor stimulation (SKF 38393, 2 mg/kg, i.p.) in the dopamine-depleted striatum. To more generally block excitatory input, tetrodotoxin (10 μtM) was infused into the striatum of rats receiving a D 1 agonist. Local infusion of tetrodotoxin had minimal effect on induction of c- fos and zif268 in the dopamine-depleted striatum. In contrast, tetrodotoxin abolished induction of c- fos and zif268 messenger RNAs by the D 2 antagonist eticlopride (0.5 mg/kg, i.p.) in both intact rats and dopamine-depleted rats receiving continuous D 2 agonist treatment (quinpirole, 0.5 mg/kg/day). The results indicate that D 1 receptor-mediated induction of immediate early genes in the dopamine-depleted striatum occurs by mechanisms that are independent of excitatory input through (±)-α-amino3-hydroxy-5-methylisoxazole-4-propionate/kainate receptors.