Evidence for intrinsic behavioural activity of the benzodiazepine antagonist, Ro15-1788, in male mice.

It would be predicted that putative benzodiazepine should be released under anxiety-provoking conditions and that behavioural changes should be observed following pretreatment with selective antagonists of the benzodiazepine receptor. To test this hypothesis, adult male albino mice were briefly exposed to a novel, brightly-illuminated arena during the dark phase of their LD cycle. Under these test conditions, Ro15-1788 (10 mg/kg) enhanced total rearing whilst, a 5-10 mg/kg, it significantly altered the normal pattern of rearing over the test session. However, at the highest dose tested (20 mg/kg), such behavioural changes were no longer apparent. A similar, though non-significant, trend was observed for locomotor activity. These data, the first to demonstrate-low-dose intrinsic activity of Ro15-1788 in mice, suggest that benzodiazepine antagonists may prove to be powerful tools in the study of the behavioural significance of the benzodiazepine receptor.