title: Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands.
abstract: Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.
authors.affiliation: Personalité et conduites adaptives,CNRS UMR 7593, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. rinaldi@cnrs-orleans.fr
authors.forename: D
authors.initials: D
authors.lastname: Rinaldi
authors.forename: B
authors.initials: B
authors.lastname: Boutrel
authors.forename: J
authors.initials: J
authors.lastname: Adrien
authors.forename: P
authors.initials: P
authors.lastname: Venault
authors.forename: G
authors.initials: G
authors.lastname: Chapouthier
authors.forename: B
authors.initials: B
authors.lastname: Boutre
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D002243:Carbolines; D003292:Convulsants; D018755:GABA Agonists; D011963:Receptors, GABA-A; C036150:beta-carboline-3-carboxylic acid methyl ester