Convulsive effects of a benzodiazepine receptor inverse agonist: are they related to anxiogenic processes?

The linkage-testing strain of ABP/Le mice carries six mutations which express in easily identifiable phenotypes. By crossing this strain with a traditional inbred strain (C57BL/6ByJ) which is the 'wild type' for the mutated ABP/Le loci, we produced Mendelian populations, intercrosses and backcrosses so as to estimate whether the sensitivity to methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine receptor inverse agonist, and anxiety-related behaviour could be related to a common genetically determined substrate. We have shown that one locus on chromosome 9 is associated with beta-CCM-induced seizures and three loci on chromosomes 4, 7 and 9 are associated with anxiogenic processes. Analysis of [3H]flumazenil binding suggested a possible involvement of a Bmax decrease in both beta-CCM-induced seizures and anxiogenic processes. The putative common genetic regulation of both mechanisms is discussed.