The effects of flumazenil, Ro 15-4513 and beta-CCM on the behaviour of control and stressed mice in the plus-maze test.

The effects of the benzodiazepine receptor antagonist flumazenil (Ro 15-1799), the benzodiazepine receptor partial inverse agonist Ro 15-4513 and the benzodiazepine receptor inverse agonist beta-CCM on the behaviour of control and small platform stressed mice studied. Small platform stress was induced by placing the animals on small platforms (d = 3.5 cm) surrounded by water for 24 hours. This technique involves several factors of stress such as rapid eye movement sleep-deprivation, isolation, immobilization, falling into the water and soaking. In the plus-maze test small platform stress induced changes indicating anxiolytic action-an increase of the percentage of entries made onto and the percentage of time spent on the open arms. In control mice flumazenil (2.0 and 10.0 mg/kg), Ro 15-4513 (0.5; 1.0; 2.5; 5.0 and 10.0 mg/kg), and beta-CCM (1.0 and 2.0 mg/kg) exerted dose-dependent anxiogenic effect. The small platform stress induced an enhancement of the anxiogenic effect of flumazenil, but not that of Ro 15-4513 and beta-CCM. The selective enhancement of flumazenil's action may be explained with the mode of action of flumazenil. It is proposed that small platform stress causes changes in the concentration of the endogenous benzodiazepine receptor ligand with stress protective activity and flumazenil acts by blocking the effects of this endogenous ligand.