Abstract
G-protein-activated inwardly rectifying potassium channel (GIRK channel) mediates the signaling of various addictive substances. Four GIRK channel subunits (GIRK1~4) have been identified in mammals ; GIRK1~3 subunits are widely distributed in the central nervous system, and GIRK4 subunit is distributed primarily in the heart. The present review examines roles of GIRK channels in the reward system.
The results of review indicate that (1) the difference in genetic sequence of GIRK2 subunit is associated with opioid sensitivity, (2) fluoxetine, paroxetine and ifenprodile, but not fluvoxamine, inhibit GIRK channel and reduced methamphetamine preference, and (3) the medications with GIRK channel-inhibitory capacity appear to exert a curing effect on substance dependence based on retrospective studies. Above findings suggest that GIRK channels may be key molecules in the reward system, and are expected to become target molecules for treatment of substance dependence.
