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

J. Neurochem. (2010) 114, 62-73. 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 prefron...

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Published in:Journal of neurochemistry 2010-07, Vol.114 (1), p.62-73
Main Authors: Li, Yan-Chun, Liu, Gang, Hu, Jian-Li, Gao, Wen-Jun, Huang, Yue-Qiao
Format: Article
Language:English
Subjects:
Addictive behaviors
Adult and adolescent clinical studies
Biological and medical sciences
D1 receptors
Dopamine
Drug addiction
D₁ receptors
glutamate
Inhibitor drugs
Medical sciences
Neurons
NMDA receptors
prefrontal cortex
psychiatric disorders
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Schizophrenia
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Summary:J. Neurochem. (2010) 114, 62-73. 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.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2010.06720.x