Behavioral effects of glucocorticoids during the first exposures to the forced swim stress.

Glucocorticoids facilitate coping with stress, but their high levels have been also implicated in mood disorders. Due to this duality, the role of glucocorticoid signaling in the development of the first episodes of stress-induced depression remains unclear. To address this issue, effects of the glucocorticoid signal modulation on depressive-like behavior during pretest and test Porsolt swim sessions were examined. Metyrapone (MET; 150 mg/kg, i.p.) was injected 3 h before pretest to block stress-induced increase in corticosterone levels. Dexamethasone (DEX; 0.2 mg/kg, s.c.) was applied to MET-treated rats 1 h before both pretest and test sessions. In addition to behavior during these sessions, glucocorticoid receptor (GR) expression was analyzed by immunohistochemistry 2 h after the second swim. In pretest, MET-treated rats exhibited increased latency to immobility and shortened immobility. DEX reversed the behavioral effects of MET in the pretest. In the test, animals from MET + DEX group unexpectedly exhibited an antidepressant-like behavior. Swim stress increased GR expression in the frontal cortex irrespective of the pharmacological treatment. A significant elevation in GR expression was found in the prefrontal cortex (PFC) of stressed MET + DEX-treated rats and in the PFC of unstressed rats 6 h after injection of DEX alone. The data suggest that the increase in glucocorticoid levels under swim stress during pretest directly contributes to the development of the immobility response. Transition of DEX effect from prodepressant in the pretest to an antidepressant in the test was associated with the elevation in the PFC GR expression.