Skip to main content
Log in

Ethanol dependence in mice: Direct and correlated responses to ten generations of selective breeding

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

With the goal of producing an animal model of alcohol dependence, genetic selection in mice for severity of the alcohol withdrawal syndrome is underway. Ten generations of selection have been completed, and the lines selected for severe or mild expression of the withdrawal syndrome following a 9-day ethanol treatment period are significantly different from each other. The index of selection is the unrotated first-principal-component score derived from the intercorrelations among seven different measures of severity of ethanol withdrawal. Across the generations, mice from all six closed mating populations have increased their mean consumption of alcohol considerably. This seems to be the result of natural selection operating concurrently with artificial selection. When animals from generation 9 were used to test for possible correlated responses to selection, there was an indication that animals selected for mild expression of withdrawal symptoms are also less sensitive to an acute dose of ethanol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allen, D. L., Petersen, D. R., Wilson, J. R., McClearn, G. E., and Nishimoto, T. K. (1983). Selective breeding for a multivariate index of ethanol dependence in mice: Results from the first five generations.Alcoholism: Clin. Exp. Res. 7:443–447.

    Google Scholar 

  • Belknap, J. K. (1980). Genetic factors in the effects of alcohol: Neurosensitivity, functional tolerance, and physical dependence. In Rigter, H., and Crabbe, J. C. (eds.),Alcohol Tolerance and Dependence. Elsevier/North-Holland, Amsterdam, pp. 157–180.

    Google Scholar 

  • Cicero, T. J. (1980). Animal models of alcoholism? In Eriksson, K., Sinclair, J. D., and Kiianmaa (eds.),Animal Models in Alcohol Research, Academic Press, London, pp. 99–117.

    Google Scholar 

  • Crabbe, J. C. (1983). Sensitivity to ethanol in inbred mice: Genotypic correlations among several behavioral measures.Behav. Neurosci. 97:280–289.

    PubMed  Google Scholar 

  • Crabbe, J. C., Kosobud, A., and Young, E. R. (1983a). Genetic selection for ethanol withdrawal severity: Differences in replicate mouse lines.Life Sci. 33:955–962.

    PubMed  Google Scholar 

  • Crabbe, J. C., Kosobud, A., Young, E. R., and Janowsky, J. S. (1983b). Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains.Neurobehav. Toxicol. Teratol. 5:181–187.

    PubMed  Google Scholar 

  • Crabbe, J. C., Young, E. R., and Kosobud, A. (1983c). Genetic correlations with ethanol withdrawal severity.Pharmacol. Biochem. Behav. 18:541–547.

    Google Scholar 

  • DeFries, J. C. (1981). Selective breeding for behavioral and pharmacological responses in laboratory mice. In Gershon, E. S., Matthysse, S., Breakefield, X. O., and Ciaranello, R. D. (eds.),Genetic Research Strategies for Psychobiology and Psychiatry, Boxwood Press, Pacific Grove, Calif. pp. 199–214.

    Google Scholar 

  • DeFries, J. C., Wilson, J. R., and McClearn, G. E. (1970). Open-field behavior in mice: Selection response and situational generality.Behav. Genet. 1:195–211.

    PubMed  Google Scholar 

  • DeFries, J. C., Hyde, J. S., Lynch, C., Petersen, D. R., and Roberts, R. C. (1981). The design of selection experiments. In McClearn, G. E., Deitrich, R. A., and Erwin, V. G. (eds.),Development of Animal Models as Pharmacogenetic Tools, DHHS Publication No. (ADM) 81-1133, U.S. Government Printing Office, Washington, D.C., pp. 269–275.

    Google Scholar 

  • Eriksson, K., Sinclair, J. D., and Kiianmaa, K. (1980).Animal Models in Alcohol Research, Academic Press, London.

    Google Scholar 

  • Falconer, D. S. (1960).Quantitative Genetics, Ronald Press, New York.

    Google Scholar 

  • Freund, G. (1980). Comparison of alcohol dependence, withdrawal and hangover in humans and animals. In Eriksson, K., Sinclair, J. D., and Kiianmaa, K. (eds.),Animals Models in Alcohol Research, Academic Press, London, pp. 293–308.

    Google Scholar 

  • Goldstein, D. B. (1972). The relationship of alcohol dose to intensity of withdrawal signs in mice.J. Pharmacol. Exp. Ther. 180:203–215.

    PubMed  Google Scholar 

  • Goldstein, D. B. (1973). Inherited differences in intensity of alcohol withdrawal symptoms in mice.Nature 245:154–156.

    PubMed  Google Scholar 

  • Goldstein, D. B., and Pal, N. (1971). Alcohol dependence produced in mice by inhalation of ethanol: Grading the withdrawal reaction.Science 172:288–290.

    PubMed  Google Scholar 

  • Goodwin, D. W. (1980). The genetics of alcoholism.Substance Alc. Act./Misuse 1:101–117.

    Google Scholar 

  • Goodwin, D. W., Schulsinger, F., Hermansen, L., Guze, S. B., and Winokur, G. (1973). Alcohol problems in adoptees raised apart from alcoholic biological parents.Arch. Gen. Psychiat. 28:238–243.

    PubMed  Google Scholar 

  • McClearn, G. E., Deitrich, R. A., and Erwin, V. G. (eds.) (1981).Development of Animal Models as Pharmacogenetic Tools, DHHS Publication No. (ADM) 81-1133, U.S. Goverment Printing Office, Washington, D.C.

    Google Scholar 

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

    Google Scholar 

  • McClearn, G. E., Wilson, J. R., and Petersen, D. R. (1982). Selective breeding in mice for severity of the ethanol withdrawal syndrome.Substance Alc. Act./Misuse 3:135–143.

    Google Scholar 

  • Roberts, R. C. (1981). Current perspectives on selective breeding: Theoretical aspects. In McClearn, G. E., Deitrich, R. A., and Erwin, V. G., (eds.),Development of Animal Models as Pharmacogenetic Tools, DHHS Publication No. (ADM) 81-1133, U.S. Government Printing Office, Washington, D.C., pp. 37–58.

    Google Scholar 

  • Schuckit, M. A., and Rayses, V. (1979). Ethanol ingestion: Differences in blood acetaldehyde concentrations in relatives of alcoholics and controls.Science 203:54–55.

    PubMed  Google Scholar 

  • Tabakoff, B., and Ritzman, R. F. (1979). Acute tolerance in inbred and selected lines of mice.Drug Alc. Depend. 12:87–90.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by NIAAA Grant AA-03527.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, J.R., Erwin, V.G., DeFries, J.C. et al. Ethanol dependence in mice: Direct and correlated responses to ten generations of selective breeding. Behav Genet 14, 235–256 (1984). https://doi.org/10.1007/BF01065544

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01065544

Key Words

Navigation