Dopamine Modulation of Responses Mediated by Excitatory Amino Acids in the Neostriatum

Abstract

This chapter summarizes several studies that have been designed to examine the electrophysiological interactions that occur when subtypes of dopamine (DA) and excitatory amino acid (EAA) receptors are activated simultaneously and to test the hypothesis that the direction of DA modulation is a function of both the subtype of EAA receptor and the subtype of DA receptor activated. The present findings demonstrate that the complex modulatory actions of DA are dependent on combinations of coactivation of specific subtypes of EAA and DA receptors. The chapter demonstrates that the direction of the modulatory effects of DA receptor agonists can be very predictable if the subtype of receptor activated is controlled. When N-methyl-D-aspartate (NMDA) receptors are activated, D1 DA receptor agonists potentiate excitatory responses. When non-NMDA receptors are activated, D2 DA receptor agonists attenuate excitatory responses. Application of the D2-receptor agonist, quinpirole produced inconsistent effects from cell to cell. Thus responses mediated by NMDA receptors are consistently potentiated by D1 DA agonists, while those mediated by non- NMDA receptors are consistently attenuated by D2 DA agonists. These findings are of clinical relevance since the actions of DA and EAAs have been implicated in neurological and affective disorders.