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

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Abstract

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 (US)
Pages (from-to)941-952
Number of pages12
JournalNeuron
Volume38
Issue number6
DOIs
StatePublished - Jun 19 2003

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Basal Ganglia
Cocaine
GTP-Binding Protein Regulators
Dopamine
Nucleus Accumbens
GTPase-Activating Proteins
Heterotrimeric GTP-Binding Proteins
Dopamine D2 Receptors
Dopamine Agonists
Protein Subunits
Xenopus
Knockout Mice
Oocytes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rahman, Z., Schwarz, J., Gold, S. J., Zachariou, V., Wein, M. N., Choi, K. H., ... Nestler, E. J. (2003). RGS9 modulates dopamine signaling in the basal ganglia. Neuron, 38(6), 941-952. https://doi.org/10.1016/S0896-6273(03)00321-0

RGS9 modulates dopamine signaling in the basal ganglia. / Rahman, Zia; Schwarz, Johannes; Gold, Stephen J.; Zachariou, Venetia; Wein, Marc N.; Choi, Kwang Ho; Kovoor, Abraham; Chen, Ching Kang; DiLeone, Ralph J.; Schwarz, Sigrid C.; Selley, Dana E.; Sim-Selley, Laura J.; Barrot, Michel; Luedtke, Robert R.; Self, David; Neve, Rachael L.; Lester, Henry A.; Simon, Melvin I.; Nestler, Eric J.

In: Neuron, Vol. 38, No. 6, 19.06.2003, p. 941-952.

Research output: Contribution to journalArticle

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 2003, 'RGS9 modulates dopamine signaling in the basal ganglia', Neuron, vol. 38, no. 6, pp. 941-952. https://doi.org/10.1016/S0896-6273(03)00321-0
Rahman Z, Schwarz J, Gold SJ, Zachariou V, Wein MN, Choi KH et al. RGS9 modulates dopamine signaling in the basal ganglia. Neuron. 2003 Jun 19;38(6):941-952. https://doi.org/10.1016/S0896-6273(03)00321-0
Rahman, Zia ; Schwarz, Johannes ; Gold, Stephen J. ; Zachariou, Venetia ; Wein, Marc N. ; Choi, Kwang Ho ; Kovoor, Abraham ; Chen, Ching Kang ; DiLeone, Ralph J. ; Schwarz, Sigrid C. ; Selley, Dana E. ; Sim-Selley, Laura J. ; Barrot, Michel ; Luedtke, Robert R. ; Self, David ; Neve, Rachael L. ; Lester, Henry A. ; Simon, Melvin I. ; Nestler, Eric J. / RGS9 modulates dopamine signaling in the basal ganglia. In: Neuron. 2003 ; Vol. 38, No. 6. pp. 941-952.
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