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

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.

SUBMITTER: Blednov YA

PROVIDER: S-EPMC3370096 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

Blednov Y A YA Mayfield R D RD Belknap J J Harris R A RA

Genes, brain, and behavior 20120406 4

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 ...[more]

PMID: 22405477

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Project description:ObjectiveAlcohol and cannabis co-users experience more negative alcohol consequences, but distal and mediating mechanisms of this association remain largely unstudied. Considering research suggests that individuals high in impulsivity and sensation seeking are more likely to be co-users, it is possible that co-users have more positive expectancies and become heavier drinkers, which confer risk for future negative consequences. Therefore, the current study tested prospective mediation models in which impulsive personality traits indirectly predicted negative consequences through co-use, heavier drinking, and expectancies.MethodsThe current study used data from a study of familial AUD spanning 3 waves (1995-2010). Participants (N = 567) reported on impulsivity (via the Eysenck Personality Inventory and Sensation Seeking Scale) alcohol and cannabis use, alcohol expectancies, and negative consequences. Models tested the factor structure of impulsive personality traits and whether these traits predicted future negative consequences through past-year co-use and drinking/expectancies.ResultsFactor analysis suggested two factors, sensation seeking and lack of premeditation. Sensation seeking was associated with future negative consequences indirectly through co-use and both drinking quantity and positive expectancies. Lack of premeditation was not associated with co-use, but indirectly predicted negative consequences through positive expectancies, above and beyond co-use. Sensation seeking directly predicted negative expectancies, but negative expectancies did not predict negative consequences.ConclusionsImpulsive personality traits in co-users, particularly sensation seeking, explained variance in future negative alcohol consequences via heavier drinking (behavior) and positive expectancies (cognition). Personalized interventions targeting a lack of premeditation, and sensation seeking in co-users, may interrupt a developmental trajectory toward problem drinking.

Dataset Information

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

Publications

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

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