N-methyl-D-aspartate-R1 receptor antisense oligodeoxynucleotide modulates pre- and postsynaptic expression of D2...

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.