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, Kennon (Matt) Lattal, Kari Buck

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StateAccepted/In press - 2016

Fingerprint

Inwardly Rectifying Potassium Channel
Reward
GTP-Binding Proteins
Knockout Mice
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Ethanol
Learning
Street Drugs
Metabolism
Fear
Assays
Aptitude
Heterozygote
Alcoholism
Genotype
Conditioning (Psychology)

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

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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.",
keywords = "Conditioned Place Preference, Ethanol, Fear Conditioning, GIRK Channels, Reward",
author = "Tipps, {Megan E.} and Raybuck, {Jonathan D.} and Kozell, {Laura B.} and Lattal, {Kennon (Matt)} and Kari Buck",
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T1 - G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward

AU - Tipps, Megan E.

AU - Raybuck, Jonathan D.

AU - Kozell, Laura B.

AU - Lattal, Kennon (Matt)

AU - Buck, Kari

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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