Unilateral dopamine depletion increases expression of the 2A subunit of the N-methyl-D-aspartate receptor in enkephalin-positive and enkephalin-negative neurons.

Striatal efferent neurons receive dopamine- and glutamate-utilizing afferents. Previous studies have shown that dopamine depletion increases gene expression in striatopallidal neurons and decreases it in striatonigral neurons. Previous work has also reported increased expression of the 2A subunit of the N-methyl-D-aspartate receptor in the dopamine-depleted striatum. The purpose of this study therefore was to determine whether dopamine depletion differentially alters the expression of the 2A subunit of the N-methyl-D-aspartate receptor in rat striatal neurons. 6-Hydroxydopamine (8microg/2microl) was infused unilaterally into the medial forebrain bundle. Rats were killed three weeks later. Double-label in situ hybridization was performed using an 35S-labeled ribonucleotide probe directed against the messenger RNA of the 2A subunit and a digoxigenin-labeled ribonucleotide probe directed towards preproenkephalin messenger RNA to mark striatopallidal neurons. Analysis of single-labeled film autoradiograms revealed a significant increase in the expression of 2A subunit messenger RNA in the ipsilateral, but not the contralateral, striatum of dopamine-depleted animals, consistent with other studies in the literature. Cellular analysis of 2A subunit expression indicated that as a consequence of dopamine depletion there is a significant increase in the expression of this subunit in both enkephalin-positive and enkephalin-negative neurons. From this study we conclude that dopamine depletion increases messenger RNA expression of the 2A subunit of the N-methyl-D-aspartate receptor in striatopallidal and presumed striatonigral (enkephalin-negative) neurons. Such alterations may affect the pharmacology and function of the resultant receptor, and thus alter glutamate transmission in both populations of medium spiny neurons after dopamine depletion.