Studies were designed to examine the hypothesis that genetic based differences in sensitivity to several behavioral effects of ethanol are mediated, in part, by shared genes and that some of ethanol's actions are mediated by brain neurotensinergic processes. In these studies we have used recombinant inbred (RI) strains of mice derived from Long Sleep (LS/Ibg) and Short Sleep (SS/Ibg) lines of mice. The LS and SS mice were selectively bred to differ in hypnotic sensitivity but also differ in hypothermia and locomotor effects of ethanol. Therefore LSxSS RI strains were used to answer the question whether there are shared genetic influences on these diverse ethanol actions. Moreover, since the LS and SS mice were found to differ in neurotensin (NT) receptor densities in various brain regions, the LSxSS RI strains were used to determine associations between NT receptor densities and ethanol actions. The results showed a significant genetic correlation (r=.38) between hypnotic sensitivity and low-dose locomotor effects of ethanol and indicated multigenetic influences, with estimates of seven, four and three genes being responsible for mediating differences in hypnotic, hypothermic, and locomotor effects of ethanol, respectively. The findings are consistent with one or more genes having pleiotropic effects on these ethanol actions.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Campbell, A. D., Jones, B. C. and Erwin, V. G. (1991). Regional characterization of brain neurotensin receptor subtypes in LS and SS mice.Alcohol. Clin. Exp. Res. 15:1011–1017.
Cloninger, C. R. (1987). Neurogenetic adaptive mechanisms in alcoholism.Science 236:410–416.
Crabbe, J. C. (1983). Sensitivity to ethanol in inbred mice: Genotypic correlations among several behavioral responses.Behav. Neurosci. 97:280–289.
Crabbe, J. C., Janowsky, J. S., Young, E. R., and Rigter, H. (1980). Strain-specific effects of ethanol on open field activity in inbred mice.Subst. Alc. Act./Mis. 1:537–543.
DeFries, J. C., Wilson, J. R., Erwin, V. G., and Petersen, D. R. (1989). LSXSS Recombinant inbred strains of mice: Initial characterization.Alcohol. Clin. Exp. Res. 13:196–200.
Deitrich, R. A., Dunwiddie, T. V., Harris, A. R., and Erwin, V. G. (1989). Mechanisms of action of ethanol: Initial central nervous system actions.Pharmacol Rev. 41:489–537.
Dudek, B. C., and Abbott, M. E. (1984a). A biometric genetic analysis of ethanol response in selectively bred long-sleep and short-sleep mice.Behav. Genet. 14:1–19.
Dudek, B. C., and Abbott, M. E. (1984b). The relationship between ethanol-induced locomotor activation and narcosis in long-sleep and short-sleep mice.Alcohol. Clin. Exp. Res. 8:272–276.
Dudek, B. C., Abbott, M. E., and Phillips, T. J. (1984). Stimulant and depressant properties of sedative-hypnotics in mice selectively bred for differential sensitivity to ethanol.Psychopharmacology 82:46–57.
Dudek, B. C., Phillips, T. J., and Hahn, M. E. (1991). Genetic analyses of the biphasic nature of the alcohol doseresponse curve.Alcohol. Clin. Exp. Res. 15:262–269.
Erwin, V. G., and Korte, A. (1988). Brain neurotensin receptors in mice bred for differences in sensitivity to ethanol.Alcohol 5:195–201.
Erwin, V. G., and McClearn, G. E. (1981). Genetic influences on alcohol consumption and actions of alcohol. In Galanter, M. (ed.),Currents in Alcoholism, Vol. III, Grune and Stratton, New York.
Erwin V. G., Su, N. C. (1989). Neurotensin and ethanol interactions on hypothermia and locomotor activity in LS and SS mice.Alcohol. Clin. Exp. Res. 13:91–94.
Erwin, V. G., Korte, A., and Marty, M. (1987). Neurotensin selectively alters ethanol-induced anesthesia in LS/igb and SS/ibg lines of mice.Brain Res. 400:80–90.
Erwin, V. G., Jones, B. C., and Radcliffe, R. A. (1990). Further characterization of LSXSS recombinant inbred strains of mice: Activating and hypothermic effects of ethanol.Alcohol. Clin. Exp. Res. 14:200–204.
Erwin, V. G., Campbell, A. D., and Jones, B. C. (1992). Interactions of ethanol with neurotensinergic processes.Ann. N.Y. Acad. Sci. 668:277–286.
Falconer, D. S. (1981).Introduction to Quantitative Genetics, ed 2., Longman, London.
Kalivas, P. W., Nemeroff, C. B., and Prange, A. J., Jr. (1982). Neuroanatomical sites of action of neurotensin.Ann. N.Y. Acad. Sci. 400:397–418.
Luttinger, D., Nemeroff, C. B., Mason, G. A., Frye, G. D., Breese, G. R., and Prange, A. J., Jr. (1981). Enhancement of ethanol-induced sedation and hypothermia by centrally administered neurotensin, B-endorphin, and bombesin.Neuropharmacology 20:305–309.
McClearn, G. E., and Kakihana, R. (1981). Selective breeding for ethanol sensitivity: Short-sleep and long-sleep mice. McClearn, G. E., Deitrich, R. A., Erwin, V. G., (eds.), InDevelopment of Animal Models as Pharmacogenetic Tools. DHHS Publication No. (ADM), 81-1133, U.S. Government Printing Office, Washington, DC.
Nemeroff, C. B., and Cain, S. T. (1985). Neurotensin-dopamine interactions in the CNS.Trends Pharmacol. Sci. 6:201–205.
Nemeroff, C. B., Luttinger, D., Hernandez, D. E., Mailman, R. B., Mason, G. A., Davis, S. D., Widerlov, E., Frye, G. D., Kilts, C. A., Beaumont, K., Breese, G. R., and Prange, A. J., Jr. (1983). Interactions of neurotensin with brain dopamine systems: Biochemical and behavioral studies.J. Pharmacol. Exp. Ther. 225:337–345.
Schuckit, M. A. (1984). Subjective responses to alcohol in sons of alcoholics and control subjects.Arch. Gen. Psychiat. 41:879–884.
Widdowson, P. S. (1987). The effect of neurotensin, TRH and the u-opioid receptor antagonist ICI 174864 on alcoholinduced narcosis in rats.Brains Res. 424:281–289.
About this article
Cite this article
Gene Erwin, V., Jones, B.C. Genetic correlations among ethanol-related behaviors and neurotensin receptors in Long Sleep (LS) × Short Sleep (SS) recombinant inbred strains of mice. Behav Genet 23, 191–196 (1993). https://doi.org/10.1007/BF01067424
- LSxSS recombinant strains