Modulation of D2R-NR2B Interactions in Response to Cocaine

Xian Yu Liu, Xiang Ping Chu, Li Min Mao, Min Wang, Hong Xiang Lan, Minghua Li, Guo Chi Zhang, Nikhil K Parelkar, Eugene E Fibuch, Michelle Haines, Kim Neve, Fang Liu, Zhi Gang Xiong, John Q. Wang

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Dopamine-glutamate interactions in the neostriatum determine psychostimulant action, but the underlying molecular mechanisms remain elusive. Here we found that dopamine stimulation by cocaine enhances a heteroreceptor complex formation between dopamine D2 receptors (D2R) and NMDA receptor NR2B subunits in the neostriatum in vivo. The D2R-NR2B interaction is direct and occurs in the confined postsynaptic density microdomain of excitatory synapses. The enhanced D2R-NR2B interaction disrupts the association of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with NR2B, reduces NR2B phosphorylation at a CaMKII-sensitive site (Ser1303), and inhibits NMDA receptor-mediated currents in medium-sized striatal neurons. Furthermore, the regulated D2R-NR2B interaction is critical for constructing behavioral responsiveness to cocaine. Our findings here uncover a direct and dynamic D2R-NR2B interaction in striatal neurons in vivo. This type of dopamine-glutamate integration at the receptor level may be responsible for synergistically inhibiting the D2R-mediated circuits in the basal ganglia and fulfilling the stimulative effect of psychostimulants.

Original languageEnglish (US)
Pages (from-to)897-909
Number of pages13
JournalNeuron
Volume52
Issue number5
DOIs
StatePublished - Dec 7 2006

Fingerprint

Cocaine
Neostriatum
Corpus Striatum
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Dopamine
Glutamic Acid
Post-Synaptic Density
Neurons
Dopamine D2 Receptors
Basal Ganglia
N-Methyl-D-Aspartate Receptors
Synapses
Phosphorylation

Keywords

  • HUMDISEASE
  • MOLNEURO
  • SYSNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Liu, X. Y., Chu, X. P., Mao, L. M., Wang, M., Lan, H. X., Li, M., ... Wang, J. Q. (2006). Modulation of D2R-NR2B Interactions in Response to Cocaine. Neuron, 52(5), 897-909. https://doi.org/10.1016/j.neuron.2006.10.011

Modulation of D2R-NR2B Interactions in Response to Cocaine. / Liu, Xian Yu; Chu, Xiang Ping; Mao, Li Min; Wang, Min; Lan, Hong Xiang; Li, Minghua; Zhang, Guo Chi; Parelkar, Nikhil K; Fibuch, Eugene E; Haines, Michelle; Neve, Kim; Liu, Fang; Xiong, Zhi Gang; Wang, John Q.

In: Neuron, Vol. 52, No. 5, 07.12.2006, p. 897-909.

Research output: Contribution to journalArticle

Liu, XY, Chu, XP, Mao, LM, Wang, M, Lan, HX, Li, M, Zhang, GC, Parelkar, NK, Fibuch, EE, Haines, M, Neve, K, Liu, F, Xiong, ZG & Wang, JQ 2006, 'Modulation of D2R-NR2B Interactions in Response to Cocaine', Neuron, vol. 52, no. 5, pp. 897-909. https://doi.org/10.1016/j.neuron.2006.10.011
Liu XY, Chu XP, Mao LM, Wang M, Lan HX, Li M et al. Modulation of D2R-NR2B Interactions in Response to Cocaine. Neuron. 2006 Dec 7;52(5):897-909. https://doi.org/10.1016/j.neuron.2006.10.011
Liu, Xian Yu ; Chu, Xiang Ping ; Mao, Li Min ; Wang, Min ; Lan, Hong Xiang ; Li, Minghua ; Zhang, Guo Chi ; Parelkar, Nikhil K ; Fibuch, Eugene E ; Haines, Michelle ; Neve, Kim ; Liu, Fang ; Xiong, Zhi Gang ; Wang, John Q. / Modulation of D2R-NR2B Interactions in Response to Cocaine. In: Neuron. 2006 ; Vol. 52, No. 5. pp. 897-909.
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