NEUROMODULATORY ACTIONS OF DOPAMINE IN THE NEOSTRIATUM ARE DEPENDENT UPON THE EXCITATORY AMINO-ACID RECEPTOR SUBTYPES ACTIVATED

In the mammalian neostriatum, dopamine modulates neuronal responses me diated by activation of excitatory amino acid receptors. The direction of this modulation varies with the specific subtype of excitatory ami no acid receptor activated. Responses evoked by iontophoretic applicat ion of glutamate (Glu) and the non-N-methyl-D-aspartate (NMDA) agonist s quisqualate and lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic a cid were significantly attenuated when dopamine was applied. In contra st, responses evoked by NMDA were markedly potentiated. The enhancemen t of NMDA-evoked excitations was mimicked by bath application of SKF 3 8393, a D1 receptor agonist. The D1 receptor antagonist SCH 23390 bloc ked the dopamine enhancement of NMDA-induced excitations. Quinpirole, a D2 receptor agonist, attenuated responses evoked by both NMDA and no n-NMDA receptor agonists. These results indicate that the complex modu latory actions of dopamine in the neostriatum are a function of the ex citatory 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 i n neurological and affective disorders.