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

Nathan R. Rustay, John Jr Crabbe

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 2004

Fingerprint

Inbred Strains Mice
artificial selection
genetic analysis
genetic techniques and protocols
ethanol
Ethanol
tolerance
mice
heritability
Ataxia
Alcoholism
drug resistance
alcohol abuse
effect
Pharmaceutical Preparations
drug
dosage

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Behavioral Neuroscience
  • Psychology(all)

Cite this

Genetic analysis of rapid tolerance to ethanol's incoordinating effects in mice : Inbred strains and artificial selection. / Rustay, Nathan R.; Crabbe, John Jr.

In: Behavior Genetics, Vol. 34, No. 4, 07.2004, p. 441-451.

Research output: Contribution to journalArticle

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