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

Andrew Dieterich,Joseph Floeder,Prachi Srivastava,Karina Stech,Benjamin A. Samuels,Aitesam Sharif,Samantha E. Yohn

doi:10.1038/s41398-019-0674-4

Abstract

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 anxiety1–4. 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.

Highlights

Mood disorders are a major burden on society and are extremely prevalent
Similar to previous reports[1], unpaired t-tests revealed that chronic CORT administration reduced overall locomotor activity in the open field (OF) (t(37) = 4.5, p < 0.001, Fig. 1b), entries into the center of the OF (t(37) = 5.5, p < 0.001, Fig. 1c), and percent time spent in the center (t(37) = 3.5, p < 0.001, Fig. 1d)
Chronic CORT increased latency to eat in novelty-suppressed feeding (NSF) (Kaplan-Meier survival, X2(2, N = 9) = 22, p < 0.0001) (Fig. 1e) in a separate cohort of Vehicle (n = 10) and CORT-administered (n = 10) mice, without affecting latency to eat in the home cage (t(18) = 0.83), p = 0.419) (Supplemental Fig. 1a), suggesting the increase in latency is not affected by group differences in hunger

Summary

Introduction

Mood disorders are a major burden on society and are extremely prevalent. An estimated 21.4% of adults in the United States experience a mood disorder at some point in their lives[5] and ~16.2 million adults experience a major depressive episode each year[6]. Instrumental behaviors associated with positive valence in rodents may have more translational value than anxiety-related approach-avoidance behaviors associated with negative valence because relatively similar instrumental behaviors can be performed in rodents and humans to study reward learning[9], outcome devaluation[10], progressive ratio[11], and probabilistic reversal learning tasks[12,13]. This conservation across species suggests that increased adoption of using positive valence behaviors in rodents might significantly accelerate therapeutic development

Methods

Results

Conclusion