chronic-stress-shifts-effort-related-choice-behavior-y-maze-barrier

Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that ...

The State University of New Jersey

Rutgers, the State University of New Jersey

Stress-related mood disorders are more prevalent in females than males, yet preclinical chronic stress paradigms were developed in male rodents and are less effective in female rodents. Here we characterize a novel chronic non-discriminatory social defeat stress (CNSDS) paradigm that results in comparable stress effects in both sexes. Male and female C57BL/6J mice were simultaneously introduced into the home cage of resident CD-1 aggressors for 10 daily 5-min sessions. CD-1 aggressors attacked males and females indiscriminately, resulting in stress resilient and susceptible subpopulations in both sexes. CD-1 aggressors attacked C57BL/6J male intruders faster and more frequently than female intruders. However, CNSDS similarly induced negative valence behaviors in SUS mice of both sexes relative to RES and CNTRL mice. Furthermore, SUS male and female mice displayed similar increases in plasma corticosterone levels following CNSDS exposure relative to pre-stress exposure levels. The estrous cycle did not impact CD-1 attack behavior or negative valence behaviors. Thus, CNSDS induces chronic stress behavioral and neuroendocrine effects in both male and female C57BL/6J mice and allows direct comparisons between sexes. Adoption of this modified social defeat paradigm will help advance the initiative to include female rodents in preclinical chronic stress research.

Chronic non-discriminatory social defeat is an effective chronic stress paradigm for both male and female 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. 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.

Article	Year
Chronic non-discriminatory social defeat is an effective chronic stress paradigm for both male and female mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology\| PubMed ID: 31493767	2019
Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice. Translational psychiatry\| PubMed ID: 31822658	2019

Andrew Dieterich

Biography

JoVE Journal Publications

Other Publications