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 language | English (US) |
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Pages (from-to) | 441-451 |
Number of pages | 11 |
Journal | Behavior genetics |
Volume | 34 |
Issue number | 4 |
DOIs | |
State | Published - Jul 2004 |
Externally published | Yes |
Keywords
- Ataxia
- Ethanol
- Mice
- Rotarod
- Selected lines
- Tolerance
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Genetics(clinical)