Following a single Inescapable Shock (IS) session animals display long-term behavioral deficits when evaluated in a subsequent active avoidance (AA) test. A functional relationship between corticosterone (CS) released by IS and the expression of passive behaviors has been suggested. CS binds to two types of central receptors, MR & GR, being MR affinity for CS about one order of magnitude lower than that of GR. The stressor induces long-lasting changes in MR & GR that are particularly relevant at the hippocampus level for the maintenance of endocrine homeostasis and for cognitive aspects of the stress response. This work aimed to study the effect of replacement with different doses of CS (20 to 400 mg/ml) to examine how different levels of circulating CS and/or selective occupation of corticosteroid receptors are related to the behavioral impairment induced by the stressor. CS was administered via the drinking water to adrenalectomized (ADX) animals before exposure to IS and until the AA test, performed 48 hs later. MR & GR levels were determined by western-blot assays on whole hippocampal extracts from cytosolic and nuclear fractions. IS lead to a decrease in hipocampal cytosolic MR and GR of sham compared to non-stressed animals. In ADX animals with high doses of CS substitution, cytosolic and nuclear MR and GR levels were comparable to those of sham stressed controls. Both the excess and absence of CS produced a similar behavioral pattern in the AA test: maximal percentage of escape failures and latency to cross. The behavioral parameters were a function of CS levels and of the receptors status in a dose-dependent fashion. The results further support the hypothesis of the hormone and its cognate receptors involvement in the behavioral sequelae induced by stress.
