THE EFFECTS OF FLUMAZENIL, RO-15-4513 AND BETA-CCM ON THE BEHAVIOR OFCONTROL AND STRESSED MICE IN THE PLUS-MAZE TEST

The effects of the benzodiazepine receptor antagonist flumazenil (Ro 1 5-1799), the benzodiazepine receptor partial inverse agonist Ro 15-451 3 and the benzodiazepine receptor inverse agonist beta-CCM on the beha viour of control and small platform stressed mice studied. Small platf orm stress was induced by placing the animals on small platforms (d = 3.5 cm surrounded by water for 24 hours. This technique involves sever al factors of stress such as rapid eye movement sleep deprivation, iso lation, immobilization, falling into the water and soaking. In the plu s-maze test small platform stress induced changes indicating anxiolyti c 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 eff ect. The small platform stress induced an enhancement of the anxiogeni c effect of flumazenil, but not that of Ro 15-4513 and beta-CCM. The s elective enhancement of flumazenil's action may be explained with the mode of action of flumazenil. It is proposed that small platform stres s causes changes in the concentration of the endogenous benzodiazepine receptor ligand with stress protective activity and flumazenil acts b y blocking the effects of this endogenous ligand.