Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum

Dev Neurosci. 1998;20(1):1-18. doi: 10.1159/000017294.


This review examines dopamine (DA) and glutamate receptor interactions in the neostriatum (NS) primarily from a neurophysiological perspective. Historically, a clear understanding of the function of DA in the NS has been difficult because it was considered a classical neurotransmitter with either excitatory or inhibitory actions and because many of the data were obtained by use of varying methodologies. When DA is considered 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 mediated 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 non-NMDA and D1 receptors are not as predictable. The mechanisms underlying 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 underlying the D2-non-NMDA receptor interaction. The functional implications of this model in setting membrane potentials, signal-to-noise ratio, plasticity and excitotoxicity are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Afferent Pathways / physiology
  • Aging / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Channels / physiology
  • Calcium Channels, L-Type
  • Cerebral Cortex / physiology
  • Cyclic AMP / physiology
  • Dopamine / physiology*
  • Dopamine Agents / pharmacology
  • Embryonic and Fetal Development / physiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / physiology*
  • Humans
  • Ion Transport / drug effects
  • Models, Neurological
  • Neostriatum / physiology*
  • Nerve Tissue Proteins / physiology*
  • Neuronal Plasticity / drug effects
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Receptors, Dopamine / classification
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / physiology*
  • Receptors, Glutamate / classification
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Signal Transduction / drug effects
  • Substantia Nigra / physiology
  • Synaptic Transmission / drug effects


  • Calcium Channels
  • Calcium Channels, L-Type
  • Dopamine Agents
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Nerve Tissue Proteins
  • Receptors, Dopamine
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Cyclic AMP
  • Calcium
  • Dopamine