The mechanism by which addictive drugs change RGS expression is not well understood but likely involves DA receptors (D1 and D2), activation of cAMP via adenylyl cyclase, PKA-dependent phosphorylation and CREB [33][34][35][36]. RGS regulation via DA receptors may be unique for RGS2, which is the only member of the RGS family found thus far to contain a cAMP-responsive promoter region. During withdrawal, when cAMP levels are elevated due to super-sensitization of adenylyl cyclase, RGS2 levels could quickly recover and exceed baseline values due to the cAMP-responsive promoter region. More studies are needed to delineate the mechanism of drug-dependent changes in RGS expression.
