Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice

Behavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety-related behaviors). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases avoidance in negative valence behaviors associated with anxiety^1–4. However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced avoidance in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces avoidance in negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.