Relationship of the effects of the benzodiazepine derivative clorazepate on corticosterone secretion with its behavioural actions. Antagonism by Ro 15-1788.

The effectiveness of Ro 15-1788, a benzodiazepine receptor antagonist, in modifying the effects of the benzodiazepine derivative clorazepate on schedule-controlled behaviour and pituitary-adrenal activity of rats was investigated. At low doses (5 mg/kg) clorazepate increased punished responding and slightly decreased basal plasma corticosterone levels. At high doses (40 mg/kg), clorazepate suppressed fixed ratio responding, raised basal plasma levels of corticosterone and reduced the stress response produced by exposure to a novel environment. Pretreatment with Ro 15-1788 blocked the behavioural and neuroendocrine effects of the high dose of clorazepate. These results suggest that both types of effects of clorazepate share a common mechanism which involves brain benzodiazepine receptors.