Chapter

Behavioral Neurobiology of Alcohol Addiction

Volume 13 of the series Current Topics in Behavioral Neurosciences pp 187-221

Date:

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

  • John C. CrabbeAffiliated withPortland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science UniversityVA Medical Center Email author 
  • , Kenneth S. KendlerAffiliated withVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University
  • , Robert J. HitzemannAffiliated withPortland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science UniversityVA Medical Center

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Abstract

A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data.

Keywords

Withdrawal Tolerance Genetic correlations Gene expression