Interaction between dopamine and glutamate receptors following treatment with NMDA receptor antagonists

Abstract

Interactions between dopamine and glutamate neurotransmission have been reported to play an important role in a number of different systems. We were interested in examining the effects of sub-chronic treatment with NMDA receptor antagonists (dizocilpine [MK-801], and 3-carboxy-piperazin-propyl phosphonic acid [CPP]) on dopamine D 1-like, dopamine D 2-like, as well as glutamate receptors of the NMDA and AMPA receptor subtypes in the neostriatum and substantia nigra of rats that had received a massive dopamine denervation at 3 days of age. Using quantitative ligand binding autoradiography, we demonstrated that the two NMDA receptor antagonists did not have different profiles of action. Furthermore, while we found a significant negative relationship between NMDA receptors and dopamine receptors (both dopamine D 1-like and D 2-like receptor subtypes) in the neostriatum, AMPA receptors were positively correlated with dopamine D 1-like binding sites in all regions investigated. These findings suggest that the interrelationship between dopamine and glutamate receptors is highly controlled and that the nigrostriatal dopamine systems play an important role in this interaction.