DOPAMINE-RECEPTOR GENE-EXPRESSION IN HIPPOCAMPUS IS DIFFERENTIALLY REGULATED BY THE NMDA RECEPTOR ANTAGONIST MK-801

Glutamate agonists have been shown to stimulate the release of dopamin e in the striatum, while the NMDA receptor antagonist MK-801 has been shown to cause an increase in extracellular dopamine in the hippocampu s. The effects of MK-801 treatment on dopamine receptor gene expressio n in the hippocampus are largely unknown. To begin to address this que stion, we treated rats with 0.3, 1.0, and 3.0 mg/kg of MK-801 daily fo r 1 week, and measured the mRNAs encoding all five of the dopamine rec eptors in the hippocampus. MK-801 caused changes in dopamine D-1, D-2, D-3, and D-4 receptor gene expression in a complex manner that sugges ts that dopamine receptor gene expression in the hippocampus may be di fferentially regulated by glutamate, via the NMDA receptor. These find ings may have implications both for understanding the pathophysiology and modifying treatment of schizophrenia.