Glucocorticoids-induced depressive-like behaviors in mice: oral ingestion of corticosterone or hydrocortisone - A comparative study.

Chronic administration of glucocorticoids is widely used to model stress-related depression in rodents. However, corticosterone, the primary endogenous glucocorticoid in rodents, is highly lipophilic and typically requires ethanol dissolution, which may confound behavioral outcomes. Hydrocortisone (cortisol) is also detectable in mouse blood and it displays a closely related dynamics under physiological and stressful conditions to corticosterone. This study compared the behavioral effects of oral exposure to hydrocortisone hemissucinate with corticosterone (dissolved in 1% ethanol) in mice. To this aim, male Swiss mice were orally exposed for 10 days to water, hydrocortisone (0.1 mg/ml), 1% ethanol, or corticosterone (0.1 mg/ml in 1% ethanol). Body weight was daily monitored. Behavioral assessments included sucrose preference, tail suspension, splash, open field, marble burying, social interaction, and object recognition tests. Our findings showed that both glucocorticoids induced body weight loss, and reduced sucrose preference and social interaction, besides impaired memory recognition. However, 1% ethanol increased immobility in the tail suspension test and influenced body weight, thus confounding the corticosterone-related effects. Anxiety-like behaviors assessed in the exploration to the center areas of the open field, and the number of marble buried in the home cage was unaffected after chronic glucocorticoid exposure. In conclusion, hydrocortisone induced depressive-like behaviors and cognitive impairment similar to those produced by corticosterone, but without solvent-related bias. These data support the use of repeated hydrocortisone exposure in drinking water as a methodological approach to induce depressive-like phenotype in mice.