Dopamine D1 receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons

Yan-Chun Li, Gang Liu, Jian-Li Hu, Wen-Jun Gao, Yueqiao Huang, Yue-Qiao (George) Huang

Research output: Contribution to journalArticlepeer-review


Understanding the interaction between dopamine and glutamate, particularly the interaction of dopamine and NMDA receptors, may enable a more rational approach to the treatment of schizophrenia, drug addiction, and other psychiatric disorders. We show that, in prefrontal cortical neurons, dopamine D1-induced enhancement of NMDA receptor function depends on rapid insertion of new NMDA receptor 2B subunits on the synaptic surface. Protein kinase A (PKA) inhibitor, but not protein kinase C (PKC) inhibitor, completely blocked dopamine D1 agonist SKF-81297-induced increase of the total expression of NMDA receptors. Furthermore, SKF-81297 failed to alter the surface expression and synaptic insertion of NMDA receptors in the presence of PKA inhibitor, phospholipase C inhibitor, PKC inhibitor, or Src family kinase inhibitor. Our data suggest that D1-mediated enhancement of NMDA current depends on the NMDA receptor trafficking through rapid synaptic insertion and both PKA and PKC signaling pathways play important roles in the regulatory process. Although both PKA and PKC mediate the D1-induced enhancement of NMDA receptors, the phospholipase C-PKC-Src pathway is only required for surface expression and new synaptic insertion of NMDA receptors.

Original languageAmerican English
JournalJournal of neurochemistry
StatePublished - Jan 1 2010


  • Animals
  • Cells
  • Cultured
  • Cyclic AMP-Dependent Protein Kinases
  • Dendrites
  • Dopamine D1
  • Excitatory Postsynaptic Potentials
  • Miniature Postsynaptic Potentials
  • N-Methyl-D-Aspartate
  • Neurons
  • Protein Transport
  • Pyramidal Cells
  • Rats
  • Receptors
  • Signal Transduction
  • Synapses
  • animal tissue
  • article
  • brain nerve cell
  • controlled study
  • cyclic AMP dependent protein kinase
  • dopamine 1 receptor
  • n methyl dextro aspartic acid receptor
  • nonhuman
  • prefrontal cortex
  • priority journal
  • protein expression
  • protein kinase C
  • rat
  • surface property
  • synapse


  • Neuroscience and Neurobiology

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