Back to Search
Start Over
Modulation of D2R-NR2B Interactions in Response to Cocaine
- Source :
-
Neuron . Dec2006, Vol. 52 Issue 5, p897-909. 13p. - Publication Year :
- 2006
-
Abstract
- Summary: 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. [Copyright &y& Elsevier]
- Subjects :
- *LOCAL anesthetics
*NEUROTRANSMITTERS
*CATECHOLAMINES
*NERVOUS system
Subjects
Details
- Language :
- English
- ISSN :
- 08966273
- Volume :
- 52
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 23280559
- Full Text :
- https://doi.org/10.1016/j.neuron.2006.10.011