Small platform stress increases

Small platform stress was induced in male BALB/c mice by placing them on small platforms (d = 3.5 cm) surrounded by water for 24 or 72 h. This experimental model contains several factors of stress, like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. After 24 h small platform stress exposure latency to sleep was measured after the administration of the benzodiazepine receptor agonist diazepam (1.0 and 2.5 mg/kg, i.p.) and the benzodiazepine receptor inverse agonist Ro 15-4513 (1.0 mg/kg, i.p.). As could be expected, diazepam significantly shortened the latency to sleep. Surprisingly the administration of Ro 15-4513 also shortened the latency to sleep. In addition [3H]Ro 15-4513 binding was measured in the cerebellum of control and small platform stressed mice. Small platform stress for 24 h did not alter the maximal number of [3H]Ro 15-4513 binding sites (Bmax) and decreased their affinity (K(D)). Small platform stress for 72 h significantly increased the number of [3H]Ro 15-4513 binding sites and decreased their affinity. These effects were due to changes in diazepam-sensitive binding. In conclusion, it could be supposed that exposure of mice to small platform stress causes changes in the function of the [3H]Ro 15-4513 binding sites, probably a shift of binding sites toward agonist conformation, that leads to changes in the effects of Ro 15-4513.