Behavioral actions of alcohol: phenotypic relations from multivariate analysis of mutant mouse data

Authors

  • Y. A. Blednov,

    1. Waggoner Center for Alcohol and Addiction Research, Section on Neurobiology, Institute for Neuroscience, Institute for Cell and Molecular Biology, University of Texas at Austin, TX, USA
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  • R. D. Mayfield,

    1. Waggoner Center for Alcohol and Addiction Research, Section on Neurobiology, Institute for Neuroscience, Institute for Cell and Molecular Biology, University of Texas at Austin, TX, USA
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  • J. Belknap,

    1. Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA
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  • R. A. Harris

    Corresponding author
    1. Waggoner Center for Alcohol and Addiction Research, Section on Neurobiology, Institute for Neuroscience, Institute for Cell and Molecular Biology, University of Texas at Austin, TX, USA
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R. A. Harris, Waggoner Center for Alcohol and Addiction Research, Section on Neurobiology, Institute for Neuroscience, Institute for Cell and Molecular Biology, University of Texas at Austin, TX 78712, USA. E-mail: harris@mail.utexas.edu

Abstract

Behavioral studies on genetically diverse mice have proven powerful for determining relationships between phenotypes and have been widely used in alcohol research. Most of these studies rely on naturally occurring genetic polymorphisms among inbred strains and selected lines. Another approach is to introduce variation by engineering single-gene mutations in mice. We have tested 37 different mutant mice and their wild-type controls for a variety (31) of behaviors and have mined this data set by K-means clustering and analysis of correlations. We found a correlation between a stress-related response (activity in a novel environment) and alcohol consumption and preference for saccharin. We confirmed several relationships detected in earlier genetic studies, including positive correlation of alcohol consumption with saccharin consumption and negative correlations with conditioned taste aversion and alcohol withdrawal severity. Introduction of single-gene mutations either eliminated or greatly diminished these correlations. The three tests of alcohol consumption used (continuous two-bottle choice and two limited access tests: drinking in the dark and sustained high alcohol consumption) share a relationship with saccharin consumption, but differ from each other in their correlation networks. We suggest that alcohol consumption is controlled by multiple physiological systems where single-gene mutations can disrupt the networks of such systems.

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