MODULATORY ACTIONS OF DOPAMINE ON NMDA RECEPTOR-MEDIATED RESPONSES ARE REDUCED IN D-1A-DEFICIENT MUTANT MICE

The role of D-1 dopamine (DA) receptors in mediating the ability of DA to modulate responses attributable to activation of NMDA receptors wa s examined in mice lacking D-1A dopamine receptors. Specifically, expe riments were designed to test the hypothesis that the ability of DA to potentiate responses mediated by activation of NMDA receptors was att ributable to activation of D-1 receptors. Based on this hypothesis, we would predict that in the D-1A mutant mouse, either DA would not indu ce enhancement of NMDA-mediated responses, or the enhancement would be severely attenuated. The results provided evidence to support the hyp othesis. In mutant mice, DA and D-1 receptor agonists did not potentia te responses mediated by activation of NMDA receptors. In contrast, in control mice, both DA and D-1 receptor agonists markedly potentiated responses mediated by activation of NMDA receptors. The effects of DA in attenuating responses mediated by activation of non-NMDA receptors also were altered in the mutant, suggesting that this action of DA may require coupling or interactions between D-1 and D-2 receptors. The p resent studies also provided an opportunity to assess some of the basi c electrophysiological and morphological properties of neostriatal neu rons in mice lacking D-1A DA receptors. Resting membrane potential, ac tion potential parameters, input resistance, excitability, somatic siz e, dendritic extent, and estimates of spine density in mutants and con trols were similar, suggesting that these basic neurophysiological and structural properties have not been changed by the loss of the D-1A D A receptor.