RGS9 modulates dopamine signaling in the basal ganglia

Zia Rahman, Johannes Schwarz, Stephen J. Gold, Venetia Zachariou, Marc N. Wein, Kwang Ho Choi, Abraham Kovoor, Ching Kang Chen, Ralph J. DiLeone, Sigrid C. Schwarz, Dana E. Selley, Laura J. Sim-Selley, Michel Barrot, Robert R. Luedtke, David Self, Rachael L. Neve, Henry A. Lester, Melvin I. Simon, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

222 Scopus citations


Regulators of G protein signaling (RGS) modulate heterotrimeric G proteins in part by serving as GTPase-activating proteins for Gα 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.

Original languageEnglish
Pages (from-to)941-952
Number of pages12
Issue number6
StatePublished - 19 Jun 2003


Dive into the research topics of 'RGS9 modulates dopamine signaling in the basal ganglia'. Together they form a unique fingerprint.

Cite this