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Response to selection for sensitivity to ethanol hypothermia: Genetic analyses

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Selective breeding has been used to produce lines of mice differing in sensitivity to the hypothermic effects of ethanol (EtOH). Two genetically independent HOT (insensitive) and two COLD (sensitive) lines are maintained along with two nonselected control (CON) lines. The breeding program is currently in selected generation 14, and HOT and COLD mice differ by about 4°C in selected hypothermic response. Estimates of heritability indicate that approximately 20% of the variance in EtOH-induced hypothermic response in mice is of additive genetic origin. Inbreeding has increased at a rate of about 1.7% per generation and no fertility problems have been detected as a result of selection. Projects designed to evaluate apparent correlated responses to selection are discussed.

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  1. Alkana, R. L., Finn, D. A., Bejanian, M., and Crabbe, J. C. (1988). Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication.Life Sci. 43:1973–1982.

  2. Crabbe, J. C. (1983). Sensitivity to ethanol in inbred mice: Genotypic correlations among several behavioral responses.Behav. Neurosci. 2:280–289.

  3. Crabbe, J. C., Kosobud, A., Young, E. R., Tam, B. R., and McSwigan, J. D. (1985). Bidirectional selection for susceptibility to ethanol withdrawal seizures inMus musculus.Behav. Genet. 15:521–536.

  4. Crabbe, J. C., Kosobud, A., Tam, B. R., Young, E. R., and Deutsch, C. M. (1987). Genetic selection of mouse lines sensitive (COLD) and resistant (HOT) to acute ethanol hypothermia.Alcohol Drug Res. 7:163–174.

  5. Crabbe, J. C., Feller, D. J., and Dorow, J. S. (1989). Sensitivity and tolerance to ethanol-induced hypothermia in genetically selected mice.J. Pharmacol. Exp. Ther. 249:456–461.

  6. Cunningham, C. L., Hawks, D. M., and Niehus, D. R. (1988). Role of hypothermia in ethanol-induced conditioned taste aversion.Psychopharmacology 95:318–322.

  7. Falconer, D. S. (1983).Introduction to Quantitative Genetics, 2nd ed., London, Longman.

  8. Feller, D. J., and Crabbe, J. C. (1990). Effect of alcohols and other hypnotics in mice selected for differential sensitivity to the hypothermic actions of ethanol (submitted for publication).

  9. Hill, W. G. (1972a). Estimation of realized heritabilities from selection experiments. I. Divergent selection.Biometrics 28:747–765.

  10. Hill, W. G. (1972b). Estimation of realized heritabilities from selection experiments. II. Selection in one direction.Biometrics 28:767–780.

  11. Howerton, T. C., O'Connor, M. F., and Collins, A. C. (1983). Lipid solubility is correlated with hypnotic and hypothermic responses of Long-Sleep (LS) and Short-Sleep (SS) mice to various depressant drugs.J. Pharmacol. Exp. Ther. 227:389–393.

  12. Mayer, J. M., Khanna, J. M., Kim, C., and Kalant, H. (1983). Differential pharmacological response to ethanol, pentobarbital and morphine in rats selectively bred for ethanol sensitivity.Psychopharmacology 81:6–9.

  13. McClearn, G. E., and Kakihana, R. (1981). Selective breeding for ethanol sensitivity: Short-Sleep and Long-Sleep mice. In McClearn, G. E., Deitrich, R. A., and Erwin, V. G. (eds.),Development of Animal Models as Pharmacogenetic Tools, Washington, D.C., USDHHS-NIAAA Research Monograph No. 6, pp. 147–159.

  14. McClearn, G. E., Wilson, J. R., and Meredith, W. (1970). The use of isogenic and heterogenic mouse stocks in behavioral research. In Lindzey, A., and Thiessen, D. D. (eds.),Contribution to Behavior-Genetic Analysis: The Mouse as a Prototype, Appleton-Century-Crofts, New York, pp. 3–22.

  15. Phillips, T. J., Feller, D. J., and Crabbe, J. C. (1989). Selected mouse lines, alcohol and behavior.Experientia 45:805–827.

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Correspondence to Tamara J. Phillips.

Additional information

Supported by grants from the Department of Veterans Affairs and by PHS-NIAAA Research Grants AA05828, AA06243, and AA06498 and PHS-NIDA Contract 271-87-8120.

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Phillips, T.J., Terdal, E.S. & Crabbe, J.C. Response to selection for sensitivity to ethanol hypothermia: Genetic analyses. Behav Genet 20, 473–480 (1990). https://doi.org/10.1007/BF01067713

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Key Words

  • ethanol
  • hypothermia
  • selection
  • HOT mice
  • COLD mice
  • heritability
  • pharmacogenetics