Depression-like behaviors induced by chronic corticosterone exposure via drinking water: Time-course analysis

Hypothalamic-pituitary-adrenal (HPA) axis activity is commonly dysregulated in stress-related psychiatric disorders. The corticosterone rat model was developed to understand the influence of stress on depression-like symptomatology. To further understand the effects of corticosterone on the development of depression-like behavior, rats were continuously exposed to corticosterone (200 μg/ml) or vehicle via drinking water daily for 21 days. The rats underwent a series of behavioral tests, and electroencephalographical recordings were performed after 7, 14, and 21 days of treatment. The measurements included immobility time (i.e., despair) in the forced swim test, locomotor activity in the open field test, sucrose consumption (i.e., anhedonia) in the sucrose preference test, and sleep-wake parameters. The rats in the 7-day corticosterone exposure group exhibited depression-like behavior, including increases in despair, anhedonia, anxiety, and sleep impairments. The rats in the 14-day corticosterone exposure group exhibited normal patterns of behavior and sleep structure. When corticosterone exposure was extended to 21 days, depression-like symptoms recurred, including despair, anhedonia, anxiety, and sleep disturbances. Overall, the present study observed U-shaped depression-like effects across 3 weeks of corticosterone exposure via drinking water.