Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated

Abstract

In the mammalian neostriatum, dopamine modulates neuronal responses mediated by activation of excitatory amino acid receptors. The direction of this modulation varies with the specific subtype of excitatory amino acid receptor activated. Responses evoked by iontophoretic application of glutamate (Glu) and the non-N-methyl-D-aspartate (NMDA) agonists quisqualate and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid were significantly attenuated when dopamine was applied. In contrast, responses evoked by NMDA were markedly potentiated. The enhancement of NMDA-evoked excitations was mimicked by bath application of SKF 38393, a D1 receptor agonist. The D1 receptor antagonist SCH 23390 blocked the dopamine enhancement of NMDA-induced excitations. Quinpirole, a D2 receptor agonist, attenuated responses evoked by both NMDA and non-NMDA receptor agonists. These results indicate that the complex modulatory actions of dopamine in the neostriatum are a function of the excitatory amino acid receptor as well as the specific dopamine receptor subtype activated. These findings are of clinical relevance since the actions of dopamine and excitatory amino acids have been implicated in neurological and affective disorders.