Psychopharmacology

, Volume 68, Issue 1, pp 89–97 | Cite as

Effects of gamma-butyrolactone, amphetamine, and haloperidol in mice differing in sensitivity to alcohol

  • Bruce C. Dudek
  • Richard J. Fanelli
Original Investigations

Abstract

Gamma-butyrolactone (GBL) induced longer loss of righting reflex in mice (LS-line) selectively bred for greater sensitivity to ethanol than in less sensitive SS-line mice. GBL also induced a three-fold greater increase of brain dopamine levels in LS than in SS mice. Among three inbred strains, GBL-induced loss of righting reflex was greater in BALB/c, and greater in DBA/2 than in C57BL/6 mice. A low dose of GBL produced biphasic effects on locomotor activity. Both an initial depressant action and a later increase in activity were greater in LS than in SS mice. These GBL effects on activity were modified in a genotypedependent fashion by amphetamine. Results of these experiments as well as greater catalepsy-inducing properties of haloperidol in SS mice suggest that genotypic influences on motor reactivity to ethanol may be modeled by GBL effects on brain dopamine systems.

Key words

Alcohol Pharmacogenetics Dopamine Gamma-butyrolactone d-Amphetamine Haloperidol 

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References

  1. Alpern, H. P., Greer, C. A.: A dopaminergic basis for the effects of amphetamine on a mouse ‘preadolescent hyperkinetic’ model. Life Sci. 21, 93–98 (1977)Google Scholar
  2. Anderson, R. A., Ritzmann, R. F., Tabakoff, B.: Formation of gamma-hydroxybutyrate in brain. J. Neurochem. 28, 633–639 (1977)Google Scholar
  3. Belknap, J. K., MacInnes, J. W., McClearn, G. E.: Ethanol sleep times and hepatic alcohol and aldehyde dehydrogenase activities in mice. Physiol. Behav. 9, 453–457 (1972)Google Scholar
  4. Blum, K., Wallace, J. E., Calhoun, W., Tabor, R. G., Eubanks, J. D.: Ethanol narcosis in mice: Serotonergic involvement. Experientia 30, 1053–1054 (1974)Google Scholar
  5. Chan, A. W. K.: Gamma aminobutyric acid in different strains of mice: Effect of ethanol. Life Sci. 19, 597–604 (1976)Google Scholar
  6. Church, A. C., Fuller, J. L., Dudek, B. C.: Salsolinol differentially affects mice selected for sensitivity to alcohol. Psychopharmacology 47, 49–52 (1976)Google Scholar
  7. Church, A. C., Fuller, J. L., Dudek, B. C.: Behavioral effects of salsolinol and ethanol on mice selected for sensitivity to ethanol. Drug Alcohol Depend. 2, 443–452 (1977)Google Scholar
  8. Collins, A. C., Lebsack, M. E., Yeager, T. N.: Mechanisms that underlie sex-linked and genotypically determined differences in the depressant actions of alcohol. Ann. NY Acad. Sci. 273, 303–316 (1976)Google Scholar
  9. Davies, J. A.: The effect of gamma-butyrolactone on locomotor activity in the rat. Psychopharmacology 47, 67–72 (1978)Google Scholar
  10. Damjanovich, R. P., MacInnes, J. W.: Factors involved in ethanol nacrosis: Analysis in mice of three inbred strains. Life Sci. 13, 55–65 (1973)Google Scholar
  11. Deitrich, R. A., Collins, A. C.: Pharmacogenetics of alcoholism. In: Alcohol and opiates: Neurochemical and behavioral mechanisms, K. Blum, ed., pp. 109–139. New York: Academic 1977Google Scholar
  12. Dudek, B. C.: Dopaminergic involvement in the genetic modulation of neurosensitivity to ethanol. Doctoral dissertation, State University of New York at Binghamton. Ann Arbor: University Microfilms 1978Google Scholar
  13. Erwin, V. G., Heston, W. D. W., McClearn, G. E., Deitrich, R. A.: Effects of hypnotics on mice genetically selected for sensitivity to ethanol. Pharmacol. Biochem. Behav. 4, 679–683 (1976)Google Scholar
  14. Gianutsos, G., Thornburg, J. E., Moore, K. E.: Differential actions of dopamine agonists and antagonists on the γ-butyrolactoneinduced increase in mouse brain dopamine. Psychopharmacology 50, 225–229 (1976)Google Scholar
  15. Ginsburg, B. E.: Genetic parameters in behavioral research. In: Behavior-Genetic analysis, J. Hirsch, ed., pp. 135–153. New York: McGraw Hill 1967Google Scholar
  16. Goldstein, D. B., Kakihana, R.: Alcohol withdrawal reactions in mouse strains selectively bred for long or short sleep times. Life Sci. 17, 981–986 (1975)Google Scholar
  17. Greer, C. A., Alpern, H. P.: Mediation of myoclonic seizures by dopamine and clonic seizures by acetylcholinic and GABA. Life Sci. 21, 385–392 (1977)Google Scholar
  18. Heston, W. D. W., Erwin, V. G., Anderson, S. M., Robbins, H.: A comparison of the effects of alcohol on mice selectively bred for differences in ethanol sleep time. Life Sci. 14, 365–370 (1974)Google Scholar
  19. Hollander, M., Wolfe, D. A. (eds.): Nonparametric statistical methods. New York: Wiley 1973Google Scholar
  20. Horowitz, G. P., Whitney, G.: Alcohol-induced conditioned aversion: Genotypic specificity in mice (Mus. musculus). J. Comp. Physiol. Psychol. 89, 340–346 (1975)Google Scholar
  21. Kakihana, R., Brown, G., McClearn, G., Tabershaw, L.: Brain sensitivity to alcohol in inbred mouse strains. Science 154, 1574–1575 (196)Google Scholar
  22. Lloyd, K. G., Hornykiewicz, O.: Catecholamines in regulation of motor function. In: Catecholamines and behavior, vol. 1, A. J. Friedhoff, ed., pp. 41–57. New York, London: Plenum 1975Google Scholar
  23. McClearn, G. E.: Genetics as a tool in alcohol research. Ann. NY Acad. Sci 197, 26–31 (1972)Google Scholar
  24. McClearn, G. E., Kakihana, R.: Selective breeding for ethanol sensitivity in mice. Behav. Genet. 3, 409–410 (1973)Google Scholar
  25. Morgenroth, V. M., III, Walters, J. R., Roth, R. M.: Dopaminergic neurons: Alteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow. Biochem. Pharmacol. 25, 655–661 (1976)Google Scholar
  26. Rawat, A. K.: Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice. J. Neurochem. 22, 915–922 (1974)Google Scholar
  27. Roth, R. M., Giarman, N. J.: γ-Hydroxybutyric acid. Distribution and metabolism. Biochem. Pharmacol. 15, 1333–1348 (1966a)Google Scholar
  28. Roth, R. M., Delgado, J. M. R., Giarman, N. J.: γ-Butyrolactone and γ-hydroxybutyric acid. The pharmacologically active form. Int. J. Neuropharmacol. 5, 421–428 (1966b)Google Scholar
  29. Roth, R. M., Walters, J. R., Aghajanian, G. K.: Effect of impulse flow on the release and synthesis of dopamine in the rat striatum. In: Prontiers in catecholamine research, E. Usdin, S. M. Snyder, eds., pp. 567–574. New York: Pergamon 1973Google Scholar
  30. Sheppard, J. S., Albersheim, P., McClearn, G. E.: Enzyme activities and ethanol preference in mice. Biochem. Genet. 2, 205–212 (1968)Google Scholar
  31. Schneider, C. W., Evans, S. K., Chenoweth, M. D., Beman, F. L.: Ethanol preference and behavioral tolerance in mice: Biochemical and neurophysiological mechanisms. J. Comp. Physiol. Psychol. 82, 466–474 (1973)Google Scholar
  32. Snead, O. C.: Gamma hydroxybutyrate. Life Sci. 20, 1935–1944 (1977)Google Scholar
  33. Spano, P. F., Prezegalinski, E.: Stimulation of serotonin by anesthetic and non-anesthetic doses of gamma-hydroxybutyrate. Pharmacol. Res. Commun. 5, 55–69 (1973)Google Scholar
  34. Sutton, I., Simmonds, M. A.: Effects of acute and chronic ethanol on the γ-aminobutyric acid system in rat brain. Biochem. Pharmacol. 22, 1685–1692 (1973)Google Scholar
  35. Walters, J. R., Roth, R. M.: Dopaminergic neurons: Alteration in the sensitivity of tyrosine hydroxylase to inhibition by endogenous dopamine after cessation of impulse flow. Biochem. Pharmacol. 25, 649–654 (1976)Google Scholar
  36. Winer, B. J.: Statistical principles in experimental design. New York: McGraw Hill 1962Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Bruce C. Dudek
    • 1
  • Richard J. Fanelli
    • 2
  1. 1.Department of PsychologyState University of New York at AlbanyAlbanyUSA
  2. 2.Department of PsychologyState University of New York at BinghamtonBinghamtonUSA

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