G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward

Megan E. Tipps, Jonathan D. Raybuck, Laura B. Kozell, K. Matthew Lattal, Kari J. Buck

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: G protein-gated inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood. Methods: We compare conditioned place preference (CPP) in GIRK3 subunit knock-out (GIRK3-/-), heterozygote (GIRK3+/-), and wild-type (WT) mice. In addition, the development of locomotor tolerance/sensitization and the effects of EtOH intoxication on associative learning (fear conditioning) are also assessed. Results: Our data show significant EtOH CPP in GIRK3-/- and GIRK3+/- mice, but not in the WT littermates. In addition, we demonstrate that these effects are not due to differences in EtOH metabolism, the development of EtOH tolerance/sensitivity, or associative learning abilities. While there were no consistent genotype differences in the fear conditioning assay, our data do show a selective sensitization of the impairing effects of EtOH intoxication on contextual learning, but no effect on cued learning. Conclusions: These findings suggest that GIRK3 plays a role in EtOH reward. Furthermore, the selectivity of this effect suggests that GIRK channels could be an effective therapeutic target for the prevention and/or treatment of alcoholism.

Original languageEnglish (US)
Pages (from-to)857-864
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Issue number4
StatePublished - Apr 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Research Society on Alcoholism.


  • Conditioned Place Preference
  • Ethanol
  • Fear Conditioning
  • GIRK Channels
  • Reward


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