Mouse inbred strain differences in ethanol drinking to intoxication

J. S. Rhodes, M. M. Ford, C. H. Yu, L. L. Brown, D. A. Finn, T. Garland, J. C. Crabbe

Research output: Contribution to journalArticlepeer-review

278 Scopus citations

Abstract

Recently, we described a simple procedure, Drinking in the Dark (DID), in which C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC) above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the home cage for 4 h early during the dark phase of the light/dark cycle. Three experiments were conducted to explore this high ethanol drinking model further. In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of ethanol drinking was different from routine water intake. In experiment 2, drinking impaired performance of C57BL/6J on the accelerating rotarod and balance beam. In experiment 3, 12 inbred strains were screened to estimate genetic influences on DID and correlations with other traits. Large, reliable differences in intake and BEC were detected among the strains, with C57BL/6J showing the highest values. Strain means were positively correlated with intake and BEC in the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but BECs reached higher levels for DID. Strain mean correlations with other traits in the Mouse Phenome Project database supported previously reported genetic relationships of high ethanol drinking with low chronic ethanol withdrawal severity and low ethanol-conditioned taste aversion. We extend these findings by showing that the correlation estimates remain relatively unchanged even after correcting for phylogenetic relatedness among the strains, thus relaxing the assumption that the strain means are statistically independent. We discuss applications of the model for finding genes that predispose pharmacologically significant drinking in mice.

Original languageEnglish (US)
Pages (from-to)1-18
Number of pages18
JournalGenes, Brain and Behavior
Volume6
Issue number1
DOIs
StatePublished - Feb 2007

Keywords

  • C57BL/6J
  • Drinking
  • Drinking pattern
  • Ethanol
  • Inbred mouse strains
  • Intoxication
  • Mouse Phenome Project
  • Pharmacogenetics
  • Phylogenetically independent contrasts

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

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