GIRK channels may also be involved in the response to psychostimulants, such as cocaine and amphetamines. SNX27, a psychostimulant-inducible protein155, specifically regulates surface expression of GIRK2c and GIRK340. GIRK2 and GIRK3 knockout mice exhibit dramatically reduced intravenous self-administration of cocaine relative to wild-type mice35, while surprisingly, the GIRK2/3 double knockout self-administer more cocaine than wild type mice suggesting compensation in the single subunit knockouts that is no longer possible in the double knockout. Elucidating the changes in GIRK signaling with psychostimulants is an exciting area for future research and may lead to further insight of the role of GIRK channels in addiction.
