Small platform stress attenuates the anxiogenic effect of diazepam withdrawal in the plus-maze test

The effect of stress on the behavioural changes caused by diazepam withdrawal was studied in mice. Diazepam (2.5 mg/kg) or vehicle was injected intraperitoneally twice a day for 2 weeks. When the last vehicle or diazepam injection had been administered to the mice, 12 h later, the mice were subjected to small platform stress exposure or left in their home cages. Small platform stress was induced by placing mice on small platforms (3.5 cm diameter) surrounded by water for 24 h. This experimental model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. The plus-maze test was carried out with stressed mice as well as with mice not subjected to stress. Small platform stress induced an anxiolytic effect and diazepam withdrawal--an anxiogenic effect in the plus-maze test. Small platform stress also attenuated the anxiogenic effect of diazepam withdrawal. On the basis of this data it was proposed that small platform stress counteracts the anxiogenic effect of diazepam withdrawal in the plus-maze test. It was also proposed that the effect of stress on the signs of benzodiazepine withdrawal depends on the characteristics and duration of stress.