Dysregulation of RGS Proteins by Psychostimulants

Regulator of G protein signaling (RGS) proteins are a class of proteins that negatively modulate GPCR-mediated G protein signaling. The distribution of subtypes of RGS proteins is brain region specific. Several subtypes of RGS proteins are present in the mesolimbic dopaminergic pathway and are subjected to modulation by psychostimulants. Acute or chronic exposure to psychostimulants induces changes in mRNA levels of RGS in a subtype-, brain region-, and time-dependent manner. The dynamic changes in the abundance of RGS proteins by psychostimulant treatment may be associated with dopamine receptor sensitization or desensitization, a potential mechanism underlying drug sensitization or tolerance. Small molecule RGS inhibitors are useful tools for studying in vivo function of RGS proteins and are potential therapeutics for the treatment of psychostimulant addiction.