beta-CCT, a selective BZ-omega(1) receptor antagonist, blocks the anti-anxiety but not the amnesic action of chlordiazepoxide in mice

The aim of this study was to test further the hypothesis that different ben zodiazepine (BZ-omega) receptor subtypes may mediate anxiolytic and amnesic effects of BZ agonists, using the selective BZ-omega(1) receptor antagonis t beta-CCT (beta-carboline-3-carboxylate t-butyl-ester). Experiments were p erformed in Swiss mice using the elevated plus-maze anxiety test and two le arning tasks - passive avoidance and the radial arm maze. In the elevated p lus-maze test, beta-CCT (30 mg/kg, i.p.) completely abolished the increase in open-arm entries induced by the BZ chlordiazepoxide (5 mg/kg, i.p.). Chl ordiazepoxide decreased retention latency in the passive avoidance step-thr ough procedure, and increased the number of errors in the radial arm maze. These effects were not modified by beta-CCT. Except for a slight, albeit si gnificant, amnesic effect in the passive avoidance test, beta-CCT was devoi d of intrinsic activity when administered alone. These results are in agree ment with previous studies using selective BZ-omega(1) agonists, and thus p rovide further evidence that BZ-omega(1) receptors may be involved in the a nxiolytic but not in the amnesic effects of BZ agonists. (C) 2000 Lippincot t Williams & Wilkins.