N-methyl- d-aspartate receptors modulate extracellular dopamine concentration and metabolism in rat hippocampus and striatum in vivo

The effects of infusingN-methyl- d-aspartate (NMDA), and the specific NMDA receptor antagonist d-2-amino-5-phosphonoproprionic acid ( d-AP5) into rat hippocampus and stiatum on extracellular dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied using intracerebral microdialysis. In striatum NMDA increased DA extracellularly in a concentration-dependent manner. Against a 10 μM concentration of NMDA the increase in striatal DA was opposed by D-AP5 (10 μM in all experiments), which when infused alone significanlty reduced DA concentration. Infusion of NMDA and DOPAC level in a complex manner, with 10 μM concentration causing a significant increase 2 h after infusion, while 100 μM NMDA caused a transcient decrease in the metabolite. None of the treatments altered striatal dialysate HVA. In hippocampus NMDA infusion decreased dialysate DA concentration-dependent manner, and the decrease caused by 10 μM NMDA was reversed by D-AP5. When given alone the antagonist was without effect. NMDA infusion elevated hippocampal dialysate DOPAC and HVA, while HVA was decreased following D-AP5 infusion. These data indicate that DA release is reginally controlled by excitatory amino acids, but in differential manner.