G Protein-Gated Potassium Channels: A Link to Drug Addiction

Trends Pharmacol Sci. 2017 Apr;38(4):378-392. doi: 10.1016/j.tips.2017.01.007. Epub 2017 Feb 7.


G protein-gated inwardly rectifying potassium (GIRK) channels are regulators of neuronal excitability in the brain. Knockout mice lacking GIRK channels display altered behavioral responses to multiple addictive drugs, implicating GIRK channels in addictive behaviors. Here, we review the effects of GIRK subunit deletions on the behavioral response to psychostimulants, such as cocaine and methamphetamine. Additionally, exposure of mice to psychostimulants produces alterations in the surface expression of GIRK channels in multiple types of neurons within the reward system of the brain. Thus, we compare the subcellular mechanisms by which drug exposure appears to alter GIRK expression in multiple cell types and provide an outlook on future studies examining the role of GIRK channels in addiction. A greater understanding of how GIRK channels are regulated by addictive drugs may enable the development of therapies to prevent or treat drug abuse.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / chemistry
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / drug effects
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology*
  • Humans
  • Long-Term Potentiation
  • Receptors, Dopamine D2 / physiology
  • Receptors, GABA-B / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Reward
  • Substance-Related Disorders / drug therapy*
  • Ventral Tegmental Area / physiology


  • Central Nervous System Stimulants
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Receptors, Dopamine D2
  • Receptors, GABA-B
  • Receptors, N-Methyl-D-Aspartate