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.
Clément
Y
Y
URA-CNRS 1957, Personnalité et conduites adaptatives, Paris, France.
Bondoux
D
D
Launay
J M
JM
Chapouthier
G
G
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics / Q000494:pharmacology; D018757:GABA Modulators / Q000493:pharmacokinetics / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D002243:Carbolines; D003292:Convulsants; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D008024:Ligands; D011963:Receptors, GABA-A; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester