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XB-ART-5116
Neuron 2003 Jun 19;386:941-52. doi: 10.1016/s0896-6273(03)00321-0.
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RGS9 modulates dopamine signaling in the basal ganglia.

Rahman Z , Schwarz J , Gold SJ , Zachariou V , Wein MN , Choi KH , Kovoor A , Chen CK , DiLeone RJ , Schwarz SC , Selley DE , Sim-Selley LJ , Barrot M , Luedtke RR , Self D , Neve RL , Lester HA , Simon MI , Nestler EJ .


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Regulators of G protein signaling (RGS) modulate heterotrimeric G proteins in part by serving as GTPase-activating proteins for Galpha subunits. We examined a role for RGS9-2, an RGS subtype highly enriched in striatum, in modulating dopamine D2 receptor function. Viral-mediated overexpression of RGS9-2 in rat nucleus accumbens (ventral striatum) reduced locomotor responses to cocaine (an indirect dopamine agonist) and to D2 but not to D1 receptor agonists. Conversely, RGS9 knockout mice showed heightened locomotor and rewarding responses to cocaine and related psychostimulants. In vitro expression of RGS9-2 in Xenopus oocytes accelerated the off-kinetics of D2 receptor-induced GIRK currents, consistent with the in vivo data. Finally, chronic cocaine exposure increased RGS9-2 levels in nucleus accumbens. Together, these data demonstrate a functional interaction between RGS9-2 and D2 receptor signaling and the behavioral actions of psychostimulants and suggest that psychostimulant induction of RGS9-2 represents a compensatory adaptation that diminishes drug responsiveness.

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Species referenced: Xenopus
Genes referenced: kcnj3 rgs9 rgs9bp suclg1

References :
Burns, From molecules to behavior: new clues for RGS function in the striatum. 2003, Pubmed