Genetic analysis of rapid tolerance to ethanol's incoordinating effects in mice: Inbred strains and artificial selection

Nathan R. Rustay, John C. Crabbe

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Ethanol tolerance, a decrease in drug responsiveness with repeated administrations, is an important diagnostic criterion for alcoholism. Rapid tolerance develops within 8-24 hours of an initial ethanol exposure and shares many similarities with chronic tolerance. The genetic contribution to rapid tolerance to ethanol-induced ataxia was estimated using a panel of inbred strains of mice. Strains differed significantly in the degree of rapid tolerance development, which had a broad-sense heritability estimate of 0.11. Artificial selection was carried out to develop lines of mice that would show High (HRT) and Low (LRT) levels of Rapid Tolerance. Starting with HS/Npt mice, derived from a systematic cross of eight inbred strains, a significant response to selection was seen in replicate 1 by the third selection generation. No difference was found in replicate 2. Heritability estimates after the fourth generation were 0.25 for HRT-1 mice and 0.06 for LRT-1 mice. HRT-1 and LRT-1 mice also differed significantly in chronic tolerance development to four doses of ethanol. These studies provide evidence for a genetic contribution to rapid tolerance and support a genetic link between rapid and chronic tolerance to ethanol's ataxic effects.

Original languageEnglish (US)
Pages (from-to)441-451
Number of pages11
JournalBehavior genetics
Volume34
Issue number4
DOIs
StatePublished - Jul 1 2004

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Keywords

  • Ataxia
  • Ethanol
  • Mice
  • Rotarod
  • Selected lines
  • Tolerance

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

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