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The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models

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Abstract

Risk for alcohol dependence in humans has substantial genetic contributions. Successful rodent models generally attempt to address only selected features of the human diagnosis. Most such models target the phenotype of oral administration of alcohol solutions, usually consumption of or preference for an alcohol solution versus water. Data from rats and mice for more than 50 years have shown genetic influences on preference drinking and related phenotypes. This paper summarizes some key findings from that extensive literature. Much has been learned, including the genomic location and possible identity of several genes influencing preference drinking. We report new information from congenic lines confirming QTLs for drinking on mouse chromosomes 2 and 9. There are many strengths of the various phenotypic assays used to study drinking, but there are also some weaknesses. One major weakness, the lack of drinking excessively enough to become intoxicated, has recently been addressed with a new genetic animal model, mouse lines selectively bred for their high and intoxicating blood alcohol levels after a limited period of drinking in the circadian dark. We report here results from a second replicate of that selection and compare them with the first replicate.

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Acknowledgments

This paper is based on a presentation at a festschrift in honor of Gerald E. McClearn at The Pennsylvania State University, May, 2009. Preparation of this manuscript was supported by three grants from the US Department of Veterans Affairs; by NIAAA Grants AA10760, AA06243, and AA016655. The HDID selection is supported by Integrative Neuroscience Initiative on Alcoholism-West consortium Grant AA013519. We thank Lauren Brown and Pamela Metten for assistance with the breeding of HDID mice. We thank Sue Burkhart-Kasch and Jeanna Wheeler for assistance with congenic study data collection.

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  1. Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA

    John C. Crabbe, Tamara J. Phillips & John K. Belknap

  2. VA Medical Center (R&D 12), Portland, OR, 97239, USA

    John C. Crabbe, Tamara J. Phillips & John K. Belknap

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  1. John C. Crabbe
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Crabbe, J.C., Phillips, T.J. & Belknap, J.K. The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models. Behav Genet 40, 737–750 (2010). https://doi.org/10.1007/s10519-010-9371-z

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