Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly.

Original languageEnglish (US)
Pages (from-to)288-292
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume25
Issue number2
StatePublished - 2001

Fingerprint

Alcoholism
Genes
Alcohols
Phenotype
Genetic Predisposition to Disease
Gene-Environment Interaction
Self Administration
Drinking
Rodentia
Animals
Experiments

Keywords

  • Epistasis
  • Gene-Environment Interaction
  • Genetic Background
  • Pharmacogenetics
  • Pleiotropy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

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abstract = "Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly.",
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