PMID- 21055728
OWN - NLM
STAT- MEDLINE
DCOM- 20110428
LR  - 20191210
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 69
IP  - 3
DP  - 2011 Feb 1
TI  - Cyclic adenosine monophosphate-independent tyrosine phosphorylation of NR2B 
      mediates cocaine-induced extracellular signal-regulated kinase activation.
PG  - 218-27
LID - 10.1016/j.biopsych.2010.08.031 [doi]
AB  - BACKGROUND: Activation of the extracellular signal-regulated kinase (ERK) in the 
      striatum is crucial for long-term behavioral alterations induced by drugs of 
      abuse. In response to cocaine, ERK phosphorylation (i.e., activation) is 
      restricted to medium-sized spiny neurons expressing dopamine D1 receptor (D1R) 
      and depends on a concomitant stimulation of D1R and glutamate 
      N-methyl-D-aspartate receptor (NMDAR). However, the mechanisms responsible for 
      this activation, especially the respective contribution of D1R and NMDAR, remain 
      unknown. METHODS: We studied striatal neurons in culture stimulated with D1R 
      agonist and/or glutamate and wild-type or genetically modified mice treated with 
      cocaine. Biochemical, immunohistochemical, and imaging studies were performed. 
      Mice were also subjected to behavioral experiments. RESULTS: Stimulation of D1R 
      cannot activate ERK by itself but potentiates glutamate-mediated calcium influx 
      through NMDAR that is responsible for ERK activation. Potentiation of NMDAR by 
      D1R depends on a cyclic adenosine monophosphate-independent signaling pathway, 
      which involves tyrosine phosphorylation of the NR2B subunit of NMDAR by Src 
      family kinases. We also demonstrate that the D1R/Src family kinases/NR2B pathway 
      is responsible for ERK activation by cocaine in vivo. Inhibition of this pathway 
      abrogates cocaine-induced locomotor sensitization and conditioned place 
      preference. CONCLUSIONS: Our results show that potentiation of NR2B-containing 
      NMDAR by D1R is necessary and sufficient to trigger cocaine-induced ERK 
      activation. They highlight a new cyclic adenosine monophosphate-independent 
      pathway responsible for the integration of dopamine and glutamate signals by the 
      ERK cascade in the striatum and for long-term behavioral alterations induced by 
      cocaine.
CI  - Copyright A(c) 2011 Society of Biological Psychiatry. Published by Elsevier Inc. 
      All rights reserved.
FAU - Pascoli, Vincent
AU  - Pascoli V
AD  - Centre National de la Recherche Scientifique Unite Mixte de Recherche, Paris, 
      France.
FAU - Besnard, Antoine
AU  - Besnard A
FAU - Herve, Denis
AU  - Herve D
FAU - Pages, Christiane
AU  - Pages C
FAU - Heck, Nicolas
AU  - Heck N
FAU - Girault, Jean-Antoine
AU  - Girault JA
FAU - Caboche, Jocelyne
AU  - Caboche J
FAU - Vanhoutte, Peter
AU  - Vanhoutte P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101104
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ro 25-6981)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 42HK56048U (Tyrosine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - I5Y540LHVR (Cocaine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cocaine/*pharmacology
MH  - Conditioning, Psychological/drug effects
MH  - Corpus Striatum/drug effects/metabolism
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
MH  - Drug Interactions
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Glutamic Acid/pharmacology
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Neurons/metabolism
MH  - Phenols/pharmacology
MH  - Phosphorylation/physiology
MH  - Piperidines/pharmacology
MH  - Receptors, Dopamine D1/physiology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Tyrosine/*metabolism
MH  - src-Family Kinases/metabolism
EDAT- 2010/11/09 06:00
MHDA- 2011/04/29 06:00
CRDT- 2010/11/09 06:00
PHST- 2010/03/31 00:00 [received]
PHST- 2010/08/11 00:00 [revised]
PHST- 2010/08/30 00:00 [accepted]
PHST- 2010/11/09 06:00 [entrez]
PHST- 2010/11/09 06:00 [pubmed]
PHST- 2011/04/29 06:00 [medline]
AID - S0006-3223(10)00915-7 [pii]
AID - 10.1016/j.biopsych.2010.08.031 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2011 Feb 1;69(3):218-27. doi: 10.1016/j.biopsych.2010.08.031. 
      Epub 2010 Nov 4.