Behavior Genetics

, Volume 24, Issue 3, pp 285–297 | Cite as

Evidence for a multigenic system controlling methyl-β-carboline-3-carboxylate (β-CCM)-induced seizures

  • Benoît Martin
  • Catherine Marchaland
  • Georges Chapouthier
  • Roland Motta
Article

Abstract

β-CCM is a β-carboline known to have properties opposite to those of benzodiazepines. Our approach was to analyze, in mice, the genetic mechanisms involved in β-CCM-induced myoclonic seizures using recombinant congenic strains and F1 hybrids issued from these strains. Our aim was to define the extent of the multigenic character of β-CCM-induced myoclonic seizures, while also evaluating the distribution of the strength of the genes implicated in this trait. The results show that the control of reactivity to β-CCM is multigenic with notable epistatic involvement.

Key Words

Recombinant congenic strains recombinant inbred strains β-carbolines methyl-β-carboline-3-carboxylate inverse agonist γ-aminobutyric acid mice 

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References

  1. Belzung, C., Misslin, R., Vogel, E., Dodd, R. H., and Chapouthier, G. (1987). Anxiogenic effects of methyl-β-carboline-3-carboxylate in a light/dark choice situation.Pharmacol. Biochem. Behav. 28:29–33.Google Scholar
  2. Bruell, J. H. (1964). Inheritance of behavioral and physiological characters of mice and the problem of heterosis.Am. Zool. 4:125–128.Google Scholar
  3. Cutting, G. R., Lu, L., Ohara, B. F., Kasch, L. M., Montroserafizadeh, C., Donovan, D. M., Shimada, S., Antonarakis, S. E., Guggino, W. B., Uhl, G. R., and Kazazian, H. H. (1991): Cloning of the gamma-aminobutyric acid (GABA) σ1 cDNA—A GABA receptor subunit highly expressed in the retina.Proc. Natl. Acad. Sci. USA 88:2673–2677.Google Scholar
  4. Démant, P. and Hart, A. A. M. (1986). Recombinant congenic strains — a new tool for analysing genetic traits determined by more than one gene.Immunogenetics 24:416–422.Google Scholar
  5. Démant, P., Van Zutphen, L. F. M., Hartt, A. A. M., and Moen, C. J. A. (1992). Congenic strains and recombinant congenic strains: Tools for genetic and functional analysis of physiological traits. In Goldowitz, D., Wahlsten, D., and Wimer, R. E. (eds.),Techniques for the Genetic Analysis of Brain and Behavior, Elsevier Science, Amsterdam, pp. 147–161.Google Scholar
  6. Desforges, C., Venault, P., Dodd, R. H., Chapouthier, G., and Roubertoux, P. L. (1989). β-Carboline-induced seizures in mice: Genetic analysis.Pharmacol. Biochem. Behav. 34:733–737.Google Scholar
  7. Groot, P. C., Moen, C. J. A., Dietrich, W., Stoye, J. P., Lander, E. S., and Démant, P. (1992). The recombinant congenic strains for analysis of multigenic traits—genetic composition.FASEB J. 6:2826–2835.Google Scholar
  8. Halle-Pannenko, O., Mary, J. Y., and Motta, R. (1986). Sex-dependent effects of non-H-2 loci on lethal GVH reaction induced across anH-2 barrier.Immunogenetics 24:217–224.Google Scholar
  9. Halle-Pannenko, O., Motta, R., and Mathe, G. (1983). Pgm-1 marker linked (non-H-2) gene(s) decrease(s) lethal GVHR developed againstH-2 antigens.Transplant. Proc. 15:1458–1462.Google Scholar
  10. Halle-Pannenko, O., Pritchard, L. L., Bruley-Rosset, M., Berumen, L., and Motta, R. (1985). Parameters involved in the induction and abrogation of the graft-versus-host reaction directed against non-H-2 antigens.Immunol. Rev. 88:59–85.Google Scholar
  11. Macdonald, R. L., and Angelotti, T. P. (1993). Native and recombinant GABA(a) receptor channels.Cell Physiol Biochem. 3:352–373.Google Scholar
  12. Martin, B., Desforges, C., and Chapouthier, G. (1991). Comparisons between patterns of convulsions induced by two β-carbolines in ten inbred strains of mice.Neurosci. Lett. 133:73–76.Google Scholar
  13. Martin, B., Marchaland, C., Phillips, J., Chapouthier, G., Spach, C., and Motta, R. (1992). Recombinant congenic strains from mice from B10.D2 and DBA/2: their contribution to behavior genetic research and application to audiogenic seizures.Behav. Genet. 22:685–701.Google Scholar
  14. Möhler, H. (1992). GABAergic synaptic transmission—regulation by drugs.Arzneimittelforschung 42:211–214.Google Scholar
  15. Motta, R., Desgrousilliers, A., and Spach, C. (1980). Histocompatibilité mineure chez la souris.Symbioses 12:251–276.Google Scholar
  16. Motta, R., Moutier, R., and Halle-Pannenko, O. (1981). Minor histocompatibility genes important in lethal graft-versus-host reaction (GVHR): Chromosomal assignment of five genes using ten chromosomal markers.Transplant. Proc. 13:1207–1214.Google Scholar
  17. Motta, R., and Spach, C. (1993). Strong allelic selection in the course of brother x sister matings in mice.J. Hered. 84:49–56.Google Scholar
  18. Motta, R., Spach, C., Desgrousilliers, A., Moutier, R., Bertrand, M.-F., Leloup, P., Motta, G., Bureaud, N., Gonzalez, M.-C., Gille, F., and Annicolas, D. (1987). Creation de 36 souches congéniques recombinantes (C.R.) entre B10.D2 et DBA/2.Sci. Tech. Anim. Lab. 12:5–17.Google Scholar
  19. Motta, R., Spach, C., Annicolas, D., Bertrand, M.-F., Bureaud, N., Desgrousilliers, A., Gille, F., Gonzalez, M.-C., Leloup, P., Motta, G., and Moutier, R. (1989). Thirtysix recombinant congenic inbred mouse strains between B10.D2 and DBA/2 strains carrying about 99% and 1% of the genetic background of each parent, respectively.Mouse News Lett. 85:11.Google Scholar
  20. Nutt, D. J., and Lister, R. G. (1988). Strain differences in response to a benzodiazepine receptor inverse agonist (FG 7142) in mice.Psychopharmacology 94:435–436.Google Scholar
  21. Olsen, R. W., and Tobin, A. J. (1990). Molecular biology of GABA-A receptors.FASEB J. 4:1469–1480.Google Scholar
  22. Prado de Carvalho, L., Grecksch, G., Chapouthier, G., and Rossier, J. (1983). Anxiogenic and non-anxiogenic benzodiazepine antagonists.Nature 301:64–66.Google Scholar
  23. Prado de Carvalho, L., Grecksch, G., Cavalheiro, E. A., Dodd, R. H., Chapouthier, G., and Rossier, J. (1984). Characterization of convulsions induced by methyl-β-carboline-3-carboxylate in mice.Eur. J. Pharmacol. 103:287–293.Google Scholar
  24. Pritchett, D. B., Luddens, H., and Seeburg, P. H. (1989). Type I and type II GABA(A)-benzodiazepine receptors produced in transfected cells.Science 245:1389–1392.Google Scholar
  25. Raffalli-Sébille, M.-J., and Chapouthier, G. (1991). Similar effects of a β-carboline and of flumazenil in negatively and positively reinforced learning tasks in mice.Life Sci. 48:685–692.Google Scholar
  26. Roubertoux, P., Nosten-Bertrand, M., and Carlier, M. (1990). Additive and interactive effects of genotype and maternal environments.Adv. Study Behav. 19:205–247.Google Scholar
  27. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Seeburg, P. H., and Barnard, E. A. (1987). Sequences and functional expression of the GABA-A receptor shows a ligand-gated receptor super-family.Nature 328:221–227.Google Scholar
  28. Seale, T. W., Abla, K. A., Roderick, T. H., Rennert, O. M., and Carney, J. M. (1987). Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM.Pharmacol. Biochem. Behav. 27:451–456.Google Scholar
  29. Shivers, B. D., Killisch, I., Sprengel, L., Sontheimer, H., Köhler, M., Schofield, P. R., and Seeburg, P. H. (1989). Two novel GABA-A receptor subunits exist in distinct neuronal subpopulations.Neuron 3:327–337.Google Scholar
  30. Sieghart, W. (1992). Molecular basis of pharmacological heterogeneity of GABA(A) receptors.Cell. Signal. 4:231–237.Google Scholar
  31. Stephenson, F. A., Duggan, M. J., and Pollard, S. (1990). The γ2 subunit is an integral component of the γ-aminobutyric acid receptor but the α1 polypeptide is the principal site of the agonist benzodiazepine photoaffinity labeling reaction.J. Biol. Chem. 265:21160–21165.Google Scholar
  32. van Zutphen, L. F. M., Denbieman, M., Lankhorst, A., and Démant, P. (1991). Segregation of genes from donor strain during the production of recombinant congenic strains.Lab. Anim. 25:193–197.Google Scholar
  33. Venault, P., Chapouthier, G., Prado de Carvalho, L., Simiand, J., Morre, M., Dodd, R. H., and Rossier, J. (1986). Benzodiazepine impairs and β-carboline enhances performance in learning and memory tasks.Nature 321:864–866.Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Benoît Martin
    • 1
  • Catherine Marchaland
    • 1
  • Georges Chapouthier
    • 1
  • Roland Motta
    • 2
  1. 1.Génétique, Neurogénétique et Comportement, URA 1294-CNRSUFR Biomédicale Paris VParis Cedex 06France
  2. 2.Laboratoire de Recherche Génétique sur les Modèles Animaux (LRGMA) (CSAL)-CNRSOrleans Cedex 2France

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