The effects of acute and chronic administration of corticosterone on rat behavior in two models of fear responses, plasma corticosterone concentration, and c-Fos expression in the brain structures

The aim of this paper was to examine changes in rat emotional behavior, and to find the brain structures, which are involved in the mediation of behavioral effects, related to the repeated administration of glucocorticoids. The effects of acute and chronic pretreatment of rats with two doses of corticosterone (5 and 20 mg/kg) were analyzed in two models of fear responses: neophobia-like behavior in the open field test, and freezing reaction in the conditioned fear test. Behavioral effects of repeated glucocorticoid administration were compared to changes in blood total corticosterone concentration, and expression of immediate early gene (c-Fos) in brain structures. It was found that acute administration of corticosterone (90 min before tests) enhanced rat exploratory behavior, and decreased freezing reaction. On the other hand, repeated administration of corticosterone (for 25 days, the final injection 90 min before contextual fear conditioning training) decreased plasma corticosterone concentration, inhibited exploratory behavior, enhanced freezing responses on retest and produced a complex pattern of changes in c-Fos expression, stimulated by exposure of rats to the aversively conditioned context. Aversive context induced c-Fos in the magnocellular neurons of the hypothalamic paraventricular nucleus (mPVN), dentate gyrus (DG), cingulate cortex area 1 (Cg1), and primary motor cortex (M1). In rats chronically treated with corticosterone this effect was attenuated in the mPVN and DG, enhanced in the M1, and additionally observed in the CA1, CA2 layers of the hippocampus, and in the central nucleus of amygdala (CeA), in comparison to control animals not subjected to contextual fear test. In sum, the present data suggest that chronic corticosterone treatment enhances the activity of primary motor cortex and CeA with subsequent improvement of memory of aversive events, and simultaneously stimulates a negative feedback mechanism operating in PVN with ensuing decrease in blood corticosterone concentration.