Dopaminergic denervation of striatum results in elevated expression of NR2A subunit

An imbalance between glutamate and dopamine in the striatum may contribute to the pathophysiology of Parkinson's disease. We therefore studied the effect of dopaminergic denervation of the rat striatum (unilateral 6-OHDA lesions of the medial forebrain bundle) on NMDA receptors. The expression of NMDA receptor genes (NR1, NR2A-B) was examined by in situ hybridization using oligonucleotide probes, and binding to NMDA receptors assessed using L-[3H]glutamate. Three weeks after lesioning, denervated striatum exhibited a selective increase (+13%) in the level of NR2A mRNA, NMDA receptor binding was unchanged. These results demonstrate that dopaminergic denervation exerts differential effects on NMDA receptor gene expression. Because the properties of NMDA receptors depend on the subunit composition, selective changes in the expression of mRNAs encoding the subunits may lead to modified NMDA receptor function.