N-methyl-D-aspartate-R1 receptor antisense oligodeoxynucleotide modulates pre- and postsynaptic expression of D2 dopamine receptors in the rat.

To elucidate the relationship between glutamatergic and dopaminergic transmissions, the effects of antisense oligodeoxynucleotide (aODN) to mRNA of NR1 subunit of N-methyl-D-aspartate (NMDA) receptors on the expression of dopamine D(2) receptors (DRD(2)) were examined. Rats received continuous intracerebroventricular administration (20 nmol /day, for 7 days) of aODN or sense ODN (sODN), or of the same amount of saline. In vitro receptor autoradiography revealed that NR1 aODN induced a significant decrease in specific [(3)H]YM-09151-2 binding in the substantia nigra as compared to sODN and saline. Non-significant decreases were also seen in the ventral tegmental area. Northern blot analysis demonstrated a significant increase in DRD(2) mRNA expression in the striata of aODN-treated animals. These results suggest that specific inhibition of NMDA receptor expression modulates pre- and post-synaptic expression of DRD(2), possibly via reduced nigrostriatal dopaminergic activity.