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

The effects of flumazenil, Ro 15-4513 and beta -CCM in the staircase test w ere studied in control and small platform (SP) stressed mice. SP stress was induced by placing mice on small platforms (3.5 cm in diameter) surrounded by water for 24 h. This model contains several factors of stress, such as rapid eye movement sleep deprivation, isolation, immobilization and falling into the water. The staircase test consisted of placing a mouse in an encl osed staircase with five steps and recording: (i) the number of rearings an d (ii) steps made during 3 min. SP stress increased the exploratory activit y of mice in the staircase test as demonstrated by an increase in the numbe r of rearings and steps made. In control mice flumazenil (2.0 and 10.0 mg/k g), Ro 15-4513 (1.0 and 3.0 mg/kg) and beta -CCM (1.0 and 2.0 mg/kg) exerte d an anxiogenic effect that was demonstrated by an increase in the number o f rearings without significant changes in the number of steps. Similar to c ontrol mice, flumazenil induced an anxiogenic effect in SP stressed mice as demonstrated by an increase in the number of rearings. However, the sedati ve effect of flumazenil as demonstrated by a decrease in the number of step s made was more pronounced in SP stressed mice. In the SP stressed mice, th e anxiogenic effect of Ro 15-4513 and beta -CCM was masked by their strong sedative effect and a decrease in both measures of exploratory activity (nu mber of rearings and number of steps). These data suggest that SP stress in duces hypersensitivity to the sedative effect of flumazenil, Ro 15-4513 and beta -CCM in the staircase test.