title: G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward.
abstract: 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.
authors.affiliation: Portland Alcohol Research Center , Portland VA Medical Center, Portland, Oregon.|Department of Behavioral Neuroscience , Oregon Health & Science University, Portland, Oregon.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Tipps
authors.affiliation: Department of Behavioral Neuroscience , Oregon Health & Science University, Portland, Oregon.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Raybuck
authors.affiliation: Portland Alcohol Research Center , Portland VA Medical Center, Portland, Oregon.|Department of Behavioral Neuroscience , Oregon Health & Science University, Portland, Oregon.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Kozell
authors.affiliation: Department of Behavioral Neuroscience , Oregon Health & Science University, Portland, Oregon.
authors.forename: K Matthew
authors.initials: KM
authors.lastname: Lattal
authors.affiliation: Portland Alcohol Research Center , Portland VA Medical Center, Portland, Oregon.|Department of Behavioral Neuroscience , Oregon Health & Science University, Portland, Oregon.
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Buck
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012201:Reward
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D000431:Ethanol
keywords: Conditioned Place Preference; Ethanol; Fear Conditioning; GIRK Channels; Reward