Preferential stimulation of extracellular release of dopamine in rat frontal cortex to striatum following competitive inhibition of the N-methyl-D-aspartate receptor.

Using a brain microdialysis technique, we have shown in the rat that local infusion of a selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755), into the medial frontal cortex via dialysis tubing caused a concentration-related increase in the extracellular release of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the cortical region. Coinfusion of a sodium channel blocker, tetrodotoxin, completely inhibited the ability of the NMDA antagonist to augment frontal dopamine metabolism. These findings suggest that dopamine neurons projecting to the frontal cortex might be under a tonic transsynaptic inhibition exerted by excitatory amino acid neurotransmission via the NMDA receptor at the level of dopamine terminal fields.