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

Interactions between dopamine and glutamate neurotransmission have been rep orted to play an important role in a number of different systems. We were i nterested in examining the effects of sub-chronic treatment with NMDA recep tor antagonists (dizocilpine [MK-801], and 3-carboxy-piperazin-propyl phosp honic acid [CPP]) on dopamine D-1-like, dopamine D-2-like, as well as gluta mate receptors of the NMDA and AMPA receptor subtypes in the neostriatum an d substantia nigra of rats that had received a massive dopamine denervation at 3 days of age. Using quantitative ligand binding autoradiography, we de monstrated that the two NMDA receptor antagonists did not have different pr ofiles of action. Furthermore, while we found a significant negative relati onship between NMDA receptors and dopamine receptors (both dopamine D-1-lik e and D-2-like receptor subtypes) in the neostriatum, AMPA receptors were p ositively correlated with dopamine D-1-like binding sites in all regions in vestigated. These findings suggest that the interrelationship between dopam ine and glutamate receptors is highly controlled and that the nigrostriatal dopamine systems play an important role in this interaction. (C) 1999 Else vier Science B.V. All rights reserved.