N-Methyl-D-aspartate receptors and release of newly-synthesized [3H]dopamine in nucleus accumbens slices and its relationship with neocortical afferences.

1. The effects of excitatory amino acid agonists on the release of newly-synthesized [3H]dopamine was examined in slices of nucleus accumbens of the rat. 2. L-glutamate and N-methyl-D-aspartate stimulated the release of newly-synthesized [3H]dopamine, which was completely inhibited by physiological concentrations of magnesium and by the selective and non-competitive antagonist MK-801. 3. Other ligands for excitatory amino acids subtype receptors, such as AMPA and kainic acid, had no effect of newly-synthesized [3H]dopamine release. 4. Frontal cortical ablation produced a significant increase on the N-methyl-D-aspartate-stimulated release of [3H]dopamine. 5. These data suggest that dopaminergic function in the rat nucleus accumbens is modulated by N-methyl-D-aspartate receptors, the sensitivity of which is determined, at least in part, by glutamatergic and/or aspartergic afferents from the frontal cortex.