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Dopamine D 1 and D 3 receptors oppositely regulate NMDA‐ and cocaine‐induced MAPK signaling via NMDA receptor phosphorylation
Author(s) -
Jiao Hongyuan,
Zhang Lu,
Gao Fenge,
Lou Danwen,
Zhang Jianhua,
Xu Ming
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04840.x
Subject(s) - creb , nmda receptor , protein kinase a , mapk/erk pathway , microbiology and biotechnology , chemistry , dopamine receptor , dopamine , phosphorylation , long term depression , receptor , biology , neuroscience , biochemistry , ampa receptor , transcription factor , gene
Development of drug addiction involves complex molecular changes in the CNS. The mitogen‐activated protein kinase (MAPK) signaling pathway plays a key role in mediating neuronal activation induced by dopamine, glutamate, and drugs of abuse. We previously showed that dopamine D 1 and D 3 receptors play different roles in regulating cocaine‐induced MAPK activation. Although there are functional and physical interactions between dopamine and glutamate receptors, little is known regarding the involvement of D 1 and D 3 receptors in modulating glutamate‐induced MAPK activation and underlying mechanisms. In this study, we show that D 1 and D 3 receptors play opposite roles in regulating N ‐methyl‐ d ‐aspartate (NMDA) ‐induced activation of extracellular signal‐regulated kinase (ERK) in the caudate putamen (CPu). D 3 receptors also inhibit NMDA‐induced activation of the c‐Jun N‐terminal kinase and p38 kinase in the CPu. NMDA‐induced activation of the NMDA‐receptor R1 subunit (NR1), Ca 2+ /calmodulin‐dependent protein kinase II and the cAMP‐response element binding protein (CREB), and cocaine‐induced CREB activation in the CPu are also oppositely regulated by dopamine D 1 and D 3 receptors. Finally, the blockade of NMDA‐receptor reduces cocaine‐induced ERK activation, and inhibits phosphorylation of NR1, Ca 2+ /calmodulin‐dependent protein kinase II, and CREB, while inhibiting ERK activation attenuates cocaine‐induced CREB phosphorylation in the CPu. These results suggest that dopamine D 1 and D 3 receptors oppositely regulate NMDA‐ and cocaine‐induced MAPK signaling via phosphorylation of NR1.