Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice

Tamara Phillips, Christina N. Lessov, Richard D. Harland, Steve R. Mitchell

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Abstract

Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BDX/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity end ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by- product of sensitization.

Original languageEnglish (US)
Pages (from-to)613-623
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume277
Issue number2
StatePublished - May 1996

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Ataxia
Ethanol
Quantitative Trait Loci
Hypnotics and Sedatives
Chromosome Mapping
Amphetamine
Cocaine
Genes
Phenotype
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice. / Phillips, Tamara; Lessov, Christina N.; Harland, Richard D.; Mitchell, Steve R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 277, No. 2, 05.1996, p. 613-623.

Research output: Contribution to journalArticle

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