Behavior Genetics

, Volume 29, Issue 1, pp 47–57 | Cite as

Selective Breeding for High and Low Alcohol Preference in Mice

  • Nicholas J. Grahame
  • T.-K. Li
  • Lawrence Lumeng

Abstract

High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, out-bred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.

Alcohol preference selective breeding taste alcohol metabolism heritability genetic differences 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Anderson, S. M., and McClearn, G. E. (1981). Ethanol consumption: Selective breeding in mice. Behav. Genet. 11:291–301.PubMedGoogle Scholar
  2. Belknap, J. K., Crabbe, J. C., and Young, E. R. (1993). Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510.PubMedGoogle Scholar
  3. Belknap, J. K., Richards, S. P., O'Toole, L. A., Helms, M. L., and Phillips, T. J. (1997). Short-term selective breeding as a tool for QTL mapping: Ethanol preference drinking in mice. Behav. Genet. 27:55–66.PubMedGoogle Scholar
  4. Carr, L., Foroud, T., Bice, P., Gobbett, T., Ivashina, J., Edenberg, H., Lumeng, L., and Li, T.-K. (1998). A quantitative trait locus for alcohol consumption in selectively bred rats. Alcohol. Clin. Exp. Res. 22:884–887.PubMedGoogle Scholar
  5. Crabbe, J. C. (1989). Genetic animal models in the study of alcoholism. Alcohol. Clin. Exp. Res. 13:120–127.PubMedGoogle Scholar
  6. Crabbe, J. C., and Li, T.-K. (1995). Genetic strategies in preclinical substance abuse research. In Bloom, F. E., and Kupfer, D. J. (eds.), Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York, pp. 799–811.Google Scholar
  7. Crabbe, J. C., Johnson, N. A., Gray, D. K., Kosobud, A., and Young, E. R. (1982). Biphasic effects of ethanol on open-field activity: Sensitivity and tolerance in C57BL/6N and DBA/2N mice. J. Comp. Physiol. Psychol. 96:440–451.PubMedGoogle Scholar
  8. Crabbe, J. C., Kosobud, A., Young, E. R., Tam, B. R., and McSwigan, J. D. (1985). Bidirectional selection for susceptibility to ethanol withdrawal seizures in Mus musculus. Behav. Genet. 15:521–536.Google Scholar
  9. Crabbe, J. C., Phillips, T. J., Kosobud, A., and Belknap, J. K. (1990). Estimation of genetic correlation: Interpretation of experiments using selectively bred and inbred animals. Alcohol. Clin. Exp. Res. 14:141–151.PubMedGoogle Scholar
  10. Crabbe, J. C., Belknap, J. K., and Buck, K. J. (1994). Genetic animal models of alcohol and drug abuse. Science 264:1715–1722.PubMedGoogle Scholar
  11. Cunningham, C. L., Niehus, J. S., and Noble, D. (1993). Species difference in sensitivity to ethanol's hedonic effects. Alcohol 10:97–102.PubMedGoogle Scholar
  12. Cunningham, C. L., Dickinson, S. D., and Okorn, D. M. (1995). Naloxone facilitates extinction but does not affect acquisition or expression of ethanol-induced conditioned place preference. Exp. Clin. Psychopharmacol. 3:330–343.Google Scholar
  13. Dudek, B. C., Phillips, T. J., and Hahn, M. E. (1991). Genetic analysis of the biphasic nature of the alcohol dose-response curve. Alcohol. Clin. Exp. Res. 15:262–269.PubMedGoogle Scholar
  14. Falconer, D. S., and Mackay, T. F. C. (1996). Introduction to Quantitative Genetics, Addison, Wesley Longman, Essex.Google Scholar
  15. Grahame, N. J., and Cunningham, C. L. (1997). Intravenous ethanol self-administration in C57BL/6J and DBA/2J mice. Alcohol. Clin. Exp. Res. 21:56–62.PubMedGoogle Scholar
  16. Grahame, N. J., Low M. J., and Cunningham, C. L. (1998). Intravenous self-administration of ethanol in beta-endorphin deficient mice. Alcohol. Clin. Exp. Res. 22:1093–1098.PubMedGoogle Scholar
  17. Grupp, L. A., Perlanski, E., Wanless, I. R., and Stewart, R. B. (1986). Voluntary alcohol intake in the hypertension prone Dahl rat. Pharmacol. Biochem. Behav. 24:1167–1174.PubMedGoogle Scholar
  18. Grupp, L. A., Kalant, H., and Leenen, F. H. (1989). Alcohol intake is inversely related to plasma renin activity in the genetically selected alcohol-preferring and-nonpreferring lines of rats. Pharmacol. Biochem. Behav. 32:1061–1063.PubMedGoogle Scholar
  19. Gahtan, E., Labounty, L. P., Wyvell, C., and Carroll, M. E. (1996). The relationships among saccharin consumption, oral ethanol, and i.v. cocaine self-administration. Pharmacol. Biochem. Behav. 53:919–925.PubMedGoogle Scholar
  20. Kampov-Polevoy, A. B., Overstreet, D. H., Rezvani, A. H., and Janowsky, D. S. (1995). Saccharin-induced increase in daily fluid intake as a predictor of voluntary alcohol intake in alcoholpreferring rats. Physiol. Behav. 57:791–795.PubMedGoogle Scholar
  21. Kampov-Polevoy, A. B., Kasheffskaya, O. P., Overstreet, D. H., Rezvani, A. H., Viglinskaya, I. V., Badistoy, B. A., Seredenin, S. B., Halikas, J. A., and Sinclair, J. D. (1996). Pain sensitivity and saccharin intake in alcohol-preferring and-nonpreferring rat strains. Physiol. Behav. 59:683–688.PubMedGoogle Scholar
  22. Li, T.-K., Lumeng, L., and Doolittle, D. P. (1993). Selective breeding for alcohol preference and associated responses. Behav. Genet. 23:163–170.PubMedGoogle Scholar
  23. Lumeng, L., Waller, M. B., McBride, W. J., and Li, T.-K. (1982). Different sensitivities to ethanol in alcohol-preferring and-nonpreferring rats. Pharmacol. Biochem. Behav. 16:125–130.PubMedGoogle Scholar
  24. Lumeng, L., Waller, M. B., McBride, W. J., and Li, T-K. (1995). Genetic influences on alcohol preference in animals. In Begleiter, H., and Kissin, B. (eds.), The Genetics of Alcoholism, Oxford University Press, New York, pp. 165–220.Google Scholar
  25. McClearn, G. E., and Rodgers, D. A. (1959). Differences in alcohol preference among inbred strains of mice. Q. J. Stud. Alcohol 20:691–695.Google Scholar
  26. McClearn, G. E., Wilson, J. R., and Meredith, W. (1970). The use of isogenic and heterogenic mouse stocks in behavioral research. In Lindsey, G., and Thiessen, D. D. (eds.), Contributions to Behavior-Genetic Analysis: The Mouse as a Prototype, Appleton-Century-Krofts, New York, pp. 3–22.Google Scholar
  27. Melo, J. A., Shendure, J., Pociask, K., and Silver, L. M. (1996). Identification of sex-specific quantitative trait loci controlling alcohol preference in C57BL/6 mice. Nature Genet. 13:147–153.PubMedGoogle Scholar
  28. Overstreet, D. H., Kampov-Polevoy, A. B., Rezvani, A. H., Murelle, L., Halikas, J. A., and Janowski, D. S. (1993). Saccharin intake predicts ethanol intake in genetically heterogeneous rats as well as different rat strains: Alcohol. Clin. Exp. Res. 17:366–369.PubMedGoogle Scholar
  29. Phillips, T. J., and Crabbe, J. C. (1991). Behavioral studies of genetic differences in alcohol action. In Crabbe, J. C., and Harris, R. A. (eds.), The Genetic Basis of Alcohol and Drug Actions, Plenum Press, New York, pp. 25–104.Google Scholar
  30. Phillips, T. J., Crabbe, J. C., Metten, P., and Belknap, J. K. (1994a). Localization of genes affecting alcohol drinking in mice. Alcohol. Clin. Exp. Res. 18:931–941.PubMedGoogle Scholar
  31. Phillips, T. J., Dickinson, S., and Burkhart-Kasch, S. (1994b). Behavioral sensitization to drug stimulant effects in C57BL/6J and DBA/2J inbred mice. Behav. Neurosci. 108:789–803.PubMedGoogle Scholar
  32. Pohorecky, L. A. (1977). Biphasic action of ethanol. Biobehav. Rev. 1:231–240.Google Scholar
  33. Razafimanalina, R., Mormede, P., and Velley, L. (1997). Alcohol consumption and gustatory hedonic profiles in Wistar-Kyoto hyper-and normoactive rat strains. Alcohol Alcohol. 32:485–491.PubMedGoogle Scholar
  34. Rodriguez, L. A., Plomin, R., Blizard, D. A., Jones, B. C., and McClearn, G. E. (1995). Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BxD recombinant inbred strains. Alcohol. Clin. Exp. Res. 19:367–373.PubMedGoogle Scholar
  35. Sinclair, J. D., Kampov-Polevoy, A., Stewart, R., and Li, T.-K. (1992). Taste preferences in rat lines selected for low and high alcohol consumption. Alcohol 9:155–1960.PubMedGoogle Scholar
  36. Stewart, R. B., Russell, R. N., Lumeng, L., Li, T.-K., and Murphy, J. M. (1994). Consumption of sweet, salty, sour, and bitter solutions by selectively bred alcohol-preferring and alcohol nonpreferring lines of rats. Alcohol. Clin. Exp. Res. 18:375–381.PubMedGoogle Scholar
  37. Tarantino, L. M., McClearn, G. E., Rodriguez, L. A., and Plomin, R. (1998). Confirmation of quantitative trait loci for alcohol preference in mice. Alcohol. Clin. Exp. Res. 22:1099–1105.PubMedGoogle Scholar
  38. von Wartburg, J.-P. (1989). Pharmacokinetics of alcohol. In Crow, K. E., and Batt, R. D. (eds.), Human Metabolism of Alcohol, Vol. J. Pharmacokinetics. Medicolegal Aspects, and General Interest, CRC Press, Boca Raton, FL, pp.9–22.Google Scholar
  39. Whitney, G., McClearn, G. E., and DeFries, J. C. (1970). Heritability of alcohol preference in laboratory mice and rats. J. Hered. 61:165–169.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Nicholas J. Grahame
    • 1
    • 2
  • T.-K. Li
    • 1
    • 2
  • Lawrence Lumeng
    • 1
  1. 1.Department of MedicineIndiana University School of Medicine and the Richard Roudebush Veterans Administration Medical CenterIndianapolisIndiana
  2. 2.Department of MedicineDiv. GIIndianapolisIndiana 46202

Personalised recommendations