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

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 m ethyl beta -carboline-3-carboxylate (beta -CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both line s' sensitivities to various physiological effects of other ligands of the G ABAA receptor. We measured diazepam-induced anxiolysis with the elevated pl us-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injection s. Results presented here show that the differential sensitivities of BS an d BR lines to beta -CCM can be extended to diazepam, picrotoxin, and pentyl enetetrazol, suggesting a genetic selection of a general sensitivity and re sistance to several ligands of the GABA(A) receptor.