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.