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RGS9 Modulates Dopamine Signaling in the Basal Ganglia

Rahman, Zia and Schwarz, Johannes and Gold, Stephen J. and Zachariou, Venetia and Wein, Marc N. and Choi, Kwang-Ho and Kovoor, Abraham and Chen, Ching-Kang and DiLeone, Ralph J. and Schwarz, Sigrid C. and Selley, Dana E. and Sim-Selley, Laura J. and Barrot, Michel and Luedtke, Robert R. and Self, David and Neve, Rachael L. and Lester, Henry A. and Simon, Melvin I. and Nestler, Eric J. (2003) RGS9 Modulates Dopamine Signaling in the Basal Ganglia. Neuron, 38 (6). pp. 941-952. ISSN 0896-6273. doi:10.1016/s0896-6273(03)00321-0.

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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.

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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2003 Cell Press. Received 18 October 2002, Revised 3 March 2003, Accepted 25 April 2003, Available online 17 April 2004. We wish to thank Dr. William Carlezon, Jr., for helpful discussions; Drs. Vadim Arshavsky, W.F. Simonds, and Andrejs Krummins for antibodies; Cathy Steffen for animal care; and Mike Cassidy, Christina Colby, and Lee Schlesinger for excellent technical support. This work was supported by grants from the National Institute on Drug Abuse (DA08227, DA05274), National Institute of Mental Health (MH66172), National Institute of General Medical Services (GM29836), the Plum Foundation, and by a gift from Ruben Mettler.
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Plum FoundationUNSPECIFIED
Issue or Number:6
Record Number:CaltechAUTHORS:20200515-125021148
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Official Citation: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, RGS9 Modulates Dopamine Signaling in the Basal Ganglia, Neuron, Volume 38, Issue 6, 2003, Pages 941-952, ISSN 0896-6273, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103237
Deposited By: Tony Diaz
Deposited On:15 May 2020 20:12
Last Modified:16 Nov 2021 18:19

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