RGS9-2: probing an intracellular modulator of behavior as a drug target

Trends Pharmacol Sci. 2009 Mar;30(3):105-11. doi: 10.1016/j.tips.2008.11.006. Epub 2009 Feb 9.


Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction. This protein negatively modulates signal transduction thus playing a key part in striatal function and resultant behavioral responses. In particular, there is evidence of important interactions with mu-opioid- and dopamine D(2)-receptor signaling pathways. Several studies indicate that manipulations of RGS9-2 levels in the striatum might greatly affect pharmacological responses. These findings indicate that treatment strategies targeting RGS9-2 levels or activity might be used to enhance responses to drugs acting at GPCRs and/or prevent undesired drug actions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects
  • Antipsychotic Agents / adverse effects
  • Central Nervous System Stimulants / adverse effects
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / prevention & control
  • Humans
  • Opioid-Related Disorders / metabolism
  • Opioid-Related Disorders / psychology
  • RGS Proteins / biosynthesis
  • RGS Proteins / physiology*
  • Receptors, Dopamine D2 / physiology
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Opioid, mu / physiology
  • Reward
  • Signal Transduction


  • Antiparkinson Agents
  • Antipsychotic Agents
  • Central Nervous System Stimulants
  • RGS Proteins
  • Receptors, Dopamine D2
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid, mu
  • regulator of g-protein signaling 9