Effects of NMDA receptor antagonists on D1 dopamine receptor-mediated changes in striatal immediate early gene expression: evidence for involvement of pharmacologically distinct NMDA receptors?

Dopamine D1 receptor regulation of striatal gene expression is dependent on N-methyl-D-aspartate (NMDA) receptors. To determine whether pharmacologically distinct NMDA receptors are differentially involved, we examined the effects of different NMDA receptor antagonists on D1-induced immediate early gene expression. Systemic administration of the channel blocking antagonists MK-801 and dextrorphan and the competitive antagonist CGS 19755 blocked gene expression induced by the D1 agonist SKF 82958. The NMDA polyamine site antagonist ifenprodil, however, potentiated the effect of SKF 82958. Since ifenprodil is selective for receptors containing the NR2B subunit, the data suggest that subtypes of NMDA receptors may be differentially involved in regulating striatal function.