Concentration-dependent dual action of locally applied N-methyl-D-aspartate on extracellular dopamine in the rat prefrontal cortex in vivo

Using microdialysis, the glutamate agonist N-methyl-D-aspartate (NMDA) was perfused for 20 min through the medial prefrontal cortex of freely moving rats, and its effects on extracellular concentrations of dopamine (DA) were determined. NMDA (1 mM) increased DA to 170-1500%, depending on the intensity and duration of the clonic forelimb jerks and convulsions that were induced. NMDA (0.1 mM), however, decreased DA to 61%. Metabolites of DA were decreased after both concentrations of NMDA. The effects of both 0.1 mM and 1 mM NMDA were blocked by 0.5 mM of the competitive NMDA-antagonist D-AP-5. The NMDA-induced decrease in release and metabolism possibly results from an indirect action via an inhibitory local interneuron or polysynaptic circuit.