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G Protein‐Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock‐Out Mice Show Enhanced Ethanol Reward
Author(s) -
Tipps Megan E.,
Raybuck Jonathan D.,
Kozell Laura B.,
Lattal K. Matthew,
Buck Kari J.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13012
Subject(s) - g protein coupled inwardly rectifying potassium channel , sensitization , associative learning , potassium channel , chemistry , protein subunit , conditioning , pharmacology , conditioned place preference , neuroscience , psychology , g protein , medicine , biochemistry , receptor , gene , statistics , mathematics
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 GIRK 3 subunit knock‐out ( GIRK 3 −/− ), heterozygote ( GIRK 3 +/− ), 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 GIRK 3 −/− and GIRK 3 +/− 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 GIRK 3 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.