Modulation of dopamine D-2 receptor expression by an NMDA receptor antagonist in rat brain

The expression of dopamine D-2 receptor mRNA was studied in rat brain follo wing microinjection of a competitive N-methyl D-aspartate (NMDA) receptor a ntagonist at the prefrontal cortex. Male Sprague-Dawley rats cannulated bil aterally into the medial prefrontal cortex were injected with a competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosph onic acid (CPP). The levels of mRNA for NMDA-R1 and dopamine D-2 receptors were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and D-2 receptor density was quantified by [H-3]spiperone binding in the co rtex and striatum of these animals. In the prefrontal cortex, the levels of NMDA-R1 receptor mRNA showed significant decrease in CPP-treated animals c ompared to control animals. However, NMDA-R1 mRNA levels in striatum remain ed unchanged in any of the experimental groups. The D-2 receptor mRNA level s and [H-3]spiroperidol binding in prefrontal cortical membranes showed no significant difference between the CPP-treated and control groups of animal s. In the striatum, a significant increase in striatal dopamine D-2 recepto r mRNA levels was shown in animals treated with CPP. The increase in D-2 mR NA level was correlated with an increase in the D-2 receptor binding sites in the striatal membranes. These results suggest a possible interaction bet ween prefrontal cortical NMDA receptors and striatal dopamine receptors.