DOPAMINE AND N-METHYL-D-ASPARTATE RECEPTOR INTERACTIONS IN THE NEOSTRIATUM

This review examines dopamine (DA) and glutamate receptor interactions in the neostriatum (NS) primarily from a neurophysiological perspecti ve. Historically, a clear understanding of the function of DA. in the NS has been difficult because it was considered a classical neurotrans mitter with either excitatory or inhibitory actions and because many o f the data were obtained by use of varying methodologies. When DA is c onsidered a neuromodulator whose role is to alter how NS cells respond to glutamatergic inputs, many of its actions can be accounted for and predicted with great accuracy within a model of receptor subtype. In this model, DA via activation of D1 receptors potentiates responses me diated by activation of N-methyl-D-aspartate (NMDA) receptors. DA via activation of D2 receptors attenuates responses mediated by activation of non-NMDA receptors. Outcomes of combinations of NMDA and D2 and no n-NMDA and DI receptors are not as predictable. The mechanisms underly ing the D1-NMDA receptor interactions appear to involve alterations in cell excitability mediated by activation of Ca2+ conductances and/or phosphorylation of NMDA receptors. Less is known about mechanisms unde rlying the D2-non-NMDA receptor interaction. The functional implicatio ns of this model in setting membrane potentials, signal-to-noise ratio , plasticity and excitotoxicity are discussed.