Corticosterone modulates fear responses and the expression of glucocorticoid receptors in the brain of high-anxiety rats.

The aim of our experiments was to assess the effect of acutely administered corticosterone on the expression of glucocorticoid receptors (GRs) in the brain of rats with high (HR) and low (LR) levels of anxiety. The rats were divided into groups according to their conditioned fear-induced freezing responses and then were subjected to a second conditioned fear session one week after the initial fear conditioning. Immunocytochemical analysis revealed that the second exposure to contextual aversive stimuli resulted in higher levels of GRs expression in cingulate cortex area 1 (Cg1), the secondary motor cortex (M2) of the prefrontal cortex and the dentate gyrus of the hippocampus (DG) in LR rats compared with HR rats. The pretreatment of HR rats with corticosterone (20mg/kg, sc) increased the expression levels of GRs in Cg1, the M2 area and the DG to the levels observed in the LR vehicle group. The increase in the GRs levels was accompanied by a significant decrease in the conditioned fear response in the HR group. The control animals that were not exposed to aversive stimuli had similar levels of receptor-related immunoreactivity in all brain regions, and corticosterone did not change these expression levels. Our results suggest that HR animals may have deficits in the expression of stress-induced GRs in the prefrontal cortex and the DG. In addition, pretreatment with corticosterone increases the expression of GRs and normalizes the fear response in HR rats.