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Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

  • John C. CrabbeEmail author
  • Kenneth S. Kendler
  • Robert J. Hitzemann
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 13)

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 

Abbreviations

AA/ANA

Alko Alcohol/Nonalcohol rat selected lines

AD

Alcohol dependence

ADH

Alcohol dehydrogenase

AFT

Acute functional tolerance

ALDH

Aldehyde dehydrogenase

BEC

Blood ethanol concentration

BLA

Basolateral amygdala

BXD RI

Recombinant inbred strains derived from crossing C57BL/6J and DBA/2J inbreds

C57BL/6J

A common inbred strain of mice

CA3

Region of hippocampus

CeA

Central nucleus of the amygdala

DBA/2J

A common inbred strain of mice

DSM-IV-R

Diagnostic and Statistical Manual of the American Psychiatric Association

FHP/FHN

Family history positive/negative

GABA

Gamma aminobutyric acid

GLAST

Gene encoding the glutamate-aspartate transporter

GLT-1

Gene encoding a glutamate transporter

GluR1,2,4

Genes encoding glutamate receptor subunits

Gnb1

Gene encoding the guanine nucleotide binding protein beta 1 subunit

GO

Gene ontology

HAFT/LAFT

High/Low Acute Functional Tolerance mouse selected lines

HAPLAP

High/Low Alcohol Preferring mouse selected lines

HDID

High Drinking in the Dark mouse selected line

HIC

Handling-induced convulsion

HT

Hypothermia

HRT/LRT

High/Low Rapid Tolerance mouse selected lines

NAc

Nucleus accumbens

P/NP

Preferring/Non-preferring rat selected lines

QTL

Quantitative trait locus/loci

Scd5

Gene encoding a stearoyl-CoA desaturase isoform

Scn4b

Gene encoding the sodium channel 4b subunit

SNP

Single nucleotide polymorphism

WDR

Withdrawal

WGCNA

Weighted gene covariance network analysis

WSP/WSR

Withdrawal Seizure-Prone/-Resistant mouse selected lines

Notes

Acknowledgments

The authors are supported by grants AA11408, AA017828, AA10760, AA13519, AA 11034 and AA 13484 from the NIH and by grants from the US Department of Veterans Affairs.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • John C. Crabbe
    • 1
    • 3
    Email author
  • Kenneth S. Kendler
    • 2
  • Robert J. Hitzemann
    • 1
    • 3
  1. 1.Portland Alcohol Research Center, Department of Behavioral NeuroscienceOregon Health & Science UniversityPortlandUSA
  2. 2.Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondUSA
  3. 3.VA Medical CenterPortlandUSA

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