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 recepto r-mediated glutamate transmission, whole-cell recordings were made from ide ntified pyramidal cells located in layers V and VI of the medial prefrontal cortex of the rat using a slice preparation. In the presence of tetrodotox in and the absence of Mg2+, a brief local application of N-methyl-D-asparta te evoked an inward current which was blocked by the N-methyl-D-aspartate a ntagonist dizocilpine maleate but not affected by the non-N-methyl-D-aspart ate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline, sugge sting that the observed current is mediated by N-methyl-D-aspartate recepto rs located on recorded cells. Bath application of dopamine produced opposit e effects on the N-methyl-D-aspartate current depending on the concentratio ns of dopamine applied. At low concentrations (<50 mu M), dopamine enhanced the N-methyl-D-aspartate current, whereas at higher concentrations, dopami ne suppressed the current. The same concentrations of dopamine did nor sign ificantly affect the inward current induced by the non-N-methyl-D-aspartate agonist alpha-amino-3-hydroxy-5-methylisoxazole-3-propionic acid. The enha ncing 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, whe reas 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 preferen tially on D-1-like receptors to promote N-methyl-D-aspartate receptor-media ted transmission, while at high concentrations dopamine also activates D-2- like receptors, leading to a suppression of the M-methyl-D-aspartate functi on. This differential modulation of N-methyl-D-aspartate function may have significant implications for understanding behaviors and disorders involvin g both cortical dopamine- and glutamate-mediated neurotransmission. (C) 199 9 IBRO. Published by Elsevier Science Ltd.