Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor.

Stress is recognized to precipitate depressive illness, yet the specific relationship between stress, glucocorticoids and depression is not well understood. We have recently shown that repeated corticosterone (CORT) injections reliably increase depression-like behavior on the forced-swim test in rats, suggesting that glucocorticoids can precipitate depressive symptomatology. The purpose of this experiment was to determine the extent to which the effects of CORT on depression-like behavior depend on (1) the dose-injected and (2) the duration of treatment. Rats received either acute or repeated injections of vehicle, 10, 20 or 40 mg/kg of CORT, and then were subjected to the forced-swim test. Serum CORT levels were assessed after the 21-day injection period, and 30 and 60 min after the onset of forced-swim testing. Repeated, but not acute, CORT injections decreased body weight and increased immobility behavior in the forced-swim test in a dose-dependent manner. In addition, all doses of repeated CORT injections suppressed CORT release after the novel stress of forced-swim testing. Our results demonstrate that glucocorticoids increase depression-like behavior in rats in a dose-dependent manner and disrupt normal HPA axis function. These results support the hypothesis that high levels of cortisol contribute to the etiology of depressive symptomatology in humans.