Demonstrating that RGS proteins participate in the adaptive response to addictive drugs suggest RGS proteins could be novel targets for treating addiction. Harnessing the change in coupling efficiency in DA neurons could provide a new avenue of research for treating addiction. For example, selective inhibition of the GAP domain in RGS2 would be expected to enhance GPCR signaling in the VTA, reducing DA neuron excitability. Alternatively, selective inhibition of RGS proteins could modify tolerance and dependence to certain drugs. More selective pharmacological tools will be needed, however, to avoid negative side-effects. Future studies developing inhibitors targeted to some of the unique domains in RGS proteins could be one solution [37]. Lastly, if RGS-dependent changes in coupling efficiency between GPCRs and other effectors are found, then RGS proteins may become interesting targets for a wide range of pathologies from drug addiction to hypertension and heart disease.
