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The Journal of Heredity 1995:86(4):274-279
© 1995 The American Genetic Association 86:274-279

research-article

Mouse Chromosomes 4 and 13 Are Involved in ß-Carboline-Induced Seizures

B. Martin, Y. Clément, P. Venault, and G. Chapouthier

Génétique, Neurogénétique et Comportement, URA 1294-CNRS, UFR Biomédicale Paris V 45 rue cles Saints-Pères, 75270 Paris Cedex 06, France

Address correspondence to Dr. Martin at the address above

Abstract

ß-Carbolines, such as methyI ß-carboline-3-carboxlate (ß-CCM), attach to the benzodiazepine receptors in the brain, but have effects completely opposite to those of benzodiazepines: ß-CCM is a convulsant at high doses, an anxiogenic at moderate doses, and enhances learning at low doses. The aim of this work was to detect some of the chromosomal segments involved in the regulation of ß-CCM-induced seizures. The method used was a derivation of the classical use of linkage-testing strains. We tested several strains and some of their intercrosses and back-crosses. For two of these strains, we obtained significant results showing that genes located on chromosomes 4 and 13, provisionally termed respectively Bis1 and Bis2, were involved in the regulation of ßi-carboline-induced seizures. Testing of these two strains with two other convulsant agents (pentylenetetrazol, which acts at the picrotoxine site of the GABA receptor complex, and strychnine, which acts at the glycinergic receptor) provided evidence that the genes implicated are not involved in general seizure processes but specifically in ß-CCM-induced seizures.


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