کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323260 1291762 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of D2R-NR2B Interactions in Response to Cocaine
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Modulation of D2R-NR2B Interactions in Response to Cocaine
چکیده انگلیسی

SummaryDopamine-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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 52, Issue 5, 7 December 2006, Pages 897–909
نویسندگان
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