Dopamine receptor gene expression in hippocampus is differentially regulated by the NMDA receptor antagonist MK-801

Abstract

Glutamate agonists have been shown to stimulate the release of dopamine in the striatum, while the NMDA receptor antagonist MK-801 has been shown to cause an increase in extracellular dopamine in the hippocampus. The effects of MK-801 treatment on dopamine receptor gene expression in the hippocampus are largely unknown. To begin to address this question, we treated rats with 0.3, 1.0, and 3.0 mg/kg of MK-801 daily for 1 week, and measured the mRNAs encoding all five of the dopamine receptors 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 suggests that dopamine receptor gene expression in the hippocampus may be differentially regulated by glutamate, via the NMDA receptor. These findings may have implications both for understanding the pathophysiology and modifying treatment of schizophrenia.