Modulation of Dopamine D<sub>2</sub> Receptor Expression by an NMDA Receptor Antagonist in Rat Brain

Abstract

The expression of dopamine D2 receptor mRNA was studied in rat brain following micro-injection of a competitive N-methyl D-aspartate (NMDA) receptor antagonist at the prefrontal cortex. Male Sprague-Dawley rats cannulated bilaterally into the medial prefrontal cortex were injected with a competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). The levels of mRNA for NMDA-R1 and dopamine D2 receptors were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and D2 receptor density was quantified by [3H]spiperone binding in the cortex and striatum of these animals. In the prefrontal cortex, the levels of NMDA-R1 receptor mRNA showed significant decrease in CPP-treated animals compared to control animals. However, NMDA-R1 mRNA levels in striatum remained unchanged in any of the experimental groups. The D2 receptor mRNA levels and [3H]spiroperidol binding in prefrontal cortical membranes showed no significant difference between the CPP-treated and control groups of animals. In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP. The increase in D2 mRNA level was correlated with an increase in the D2 receptor binding sites in the striatal membranes. These results suggest a possible interaction between prefrontal cortical NMDA receptors and striatal dopamine receptors.