Chronic corticosterone administration from adolescence through early adulthood attenuates depression-like behaviors in mice

There is evidence that depression may have a different neural basis at different ages. Although chronic stress and elevated glucocorticoid levels have been demonstrated to lead to the emergence of mood disorders, it remains unclear how moderate elevation of glucocorticoid levels in young animals influences depression-like behaviors and brain functions. To address this issue, the present study examines how chronic corticosterone (CORT) administration during adolescence and early adulthood influences depression-like behaviors, hypothalamic-pituitary-adrenal (HPA) axis response and hippocampal cell proliferation. Male mice were chronically administrated with CORT drinking water (20 mg/L) during adolescence. After two months of treatment, serum CORT levels were measured using enzyme immunoassay. Hippocampal glucocorticoid and mineralocorticoid receptors were characterized using Western blot. Tail suspension and forced swim tests were used to assess depression-related behaviors in mice. Immunohistochemistry was performed to measure bromodeoxyuridine (BrdU) incorporation in order to assess cell proliferation in the hippocampus. Our results suggest that chronic CORT administration induced a mild but not significant elevation in basal CORT levels and attenuated the physiological responses to stress. Chronic CORT administration also reduced expression of the hippocampal mineralocorticoid receptor and decreased immobility time in both the tail suspension test and the forced swim test. Moreover, chronic CORT administration increased the BrdU immunoreactivities in the hippocampus. Taken together, these findings suggest that chronic mild elevation by CORT administration during the adolescence and early adulthood attenuates depression-like behaviors.