Reversal of increased anxiety during benzodiazepine withdrawal: evidence for an anxiogenic endogenous ligand for the benzodiazepine receptor

Abstract Rats were injected daily for 21 days with water or with chlordiazepoxide hydrochloride (10 mg/kg) and then tested in the elevated plus-maze 24–30 hr after the last of their chronic injections. At this time, rats withdrawn from chlordiazepoxide showed a significant decrease in the % of time spent on the open arms, compared with controls, thus indicating enhanced anxiety. The benzodiazepine antagonist, flumazenil (Ro 15-1788, 4 mg/kg, IP 20 min before test) significantly ( p