Opposite modulation of cortical N-methyl-D-aspartate receptor-mediated responses by low and high concentrations of dopamine

To examine whether dopamine modulates cortical N-merhyl-D-aspartate receptor-mediated glutamate transmission, whole-cell recordings were made from identified pyramidal cells located in layers V and VI of the medial prefrontal cortex of the rat using a slice preparation. In the presence of tetrodotoxin and the absence of Mg2+, a brief local application of N-methyl-D-aspartate evoked an inward current which was blocked by the N-methyl-D-aspartate antagonist dizocilpine maleate but not affected by the non-N-methyl-D-aspartate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline, suggesting that the observed current is mediated by N-methyl-D-aspartate receptors located on recorded cells. Bath application of dopamine produced opposite effects on the N-methyl-D-aspartate current depending on the concentrations of dopamine applied. At low concentrations (<50 mu M), dopamine enhanced the N-methyl-D-aspartate current, whereas at higher concentrations, dopamine suppressed the current. The same concentrations of dopamine did nor significantly affect the inward current induced by the non-N-methyl-D-aspartate agonist alpha-amino-3-hydroxy-5-methylisoxazole-3-propionic acid. The enhancing effect of dopamine on the N-methyl-D-aspartate response was mimicked by the D-1 agonist SKF38393 and blocked by the D-1 antagonist SCH31966, whereas the suppressing effect was mimicked by the D-2 agonist quinpirole and blocked by the D-2 antagonist eticlopride. The above results suggest that dopamine at low concentrations acts preferentially on D-1-like receptors to promote N-methyl-D-aspartate receptor-mediated transmission, while at high concentrations dopamine also activates D-2-like receptors, leading to a suppression of the M-methyl-D-aspartate function. This differential modulation of N-methyl-D-aspartate function may have significant implications for understanding behaviors and disorders involving both cortical dopamine- and glutamate-mediated neurotransmission. (C) 1999 IBRO. Published by Elsevier Science Ltd.