Role of GIRK Channels in Addictive Substance Effects

G-protein-activated inwardly rectifying potassium (GIRK) channels are widely expressed in the central nervous system, including brain regions related to reward, and play an important role in mediating the signal transduction pathways of various addictive substances. Studies of GIRK knockout mice have suggested the involvement of GIRK channels in the mechanisms that underlie the effects of addictive substances. Human studies have shown that differences in the genetic sequence of one of the four GIRK channel subunits, GIRK2, are associated with analgesic requirements in patients who undergo major open abdominal surgery. Animal and human studies also showed the possible therapeutic effects of GIRK channel inhibitors in the treatment of methamphetamine dependence and alcoholism. These findings suggest that GIRK channels may be a key molecular target in the reward system for the treatment of addiction.