NEUROMODULATORY ACTIONS OF DOPAMINE ON SYNAPTICALLY-EVOKED NEOSTRIATAL RESPONSES IN SLICES

The present experiments were designed to further examine the hypothesi s that receptor subtype determines the direction of dopamine's (DA) ab ility to modulate neostriatal neuronal responses. We have reported tha t DA potentiates responses mediated by activation of N-methyl-d-aspart ate (NMDA) receptors, but attenuates responses mediated by activation of non-NMDA receptors in neocortex [Cepeda et al. (1992b) Synapse, 11: 330-341] and neostriatum [Cepeda et al. (1993) Proc. Natl. Acad. Sci. U.S.A., 90:9576-9580]. In these studies, responses to excitatory amino acids (EAAs) were evoked by microphoretic application of agonists. Th e present studies examined whether this differential modulation also a pplies to components of synaptic responses evoked by electrical stimul ation of neostriatal afferents and mediated by activation of specific subtypes of EAA receptors. Using brain slices, the actions of DA and i ts receptor specific agonists on components of neostriatal synaptic re sponses that were mediated either by NMDA or non-NMDA receptors were a ssessed. Responses mediated by NMDA receptors were potentiated by DA w hile those mediated by non-NMDA receptors were attenuated. These findi ngs provide further support for the hypothesis that the direction of m odulatory action of DA is determined by the specific subtype of EAA re ceptor activated. In addition, the enhancement of NMDA receptor-mediat ed responses was mimicked by application of SKF 38393, a D-1 receptor agonist. Quinpirole, a D-2 receptor agonist, consistently attenuated r esponses mediated by activation of non-NMDA receptors. Thus, the compl ex modulatory actions of DA are dependent upon combinations of co-acti vation of specific subtypes of EAA and DA receptors. These findings ar e of clinical relevance since the actions of DA and EAAs have been imp licated in neurological and affective disorders. (C) 1996 Wiley-Liss, Inc.