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

Summary

The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

Abstract

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

Introduction

Mood disorders such as depression and anxiety are highly prevalent in today’s society. Decades of work has continuously searched for improved treatments and relevant rodent models to study these complex disorders¹. Chronic stress is a contributing factor for mood disorders like depression². Therefore, chronic stress paradigms such as chronic social defeat stress (SDS) and chronic corticosterone administration (CORT) were developed in male mice and are now widely used to assess the neurobiological and behavioral effects of chronic stress exposure. The most widely used behavioral tests for assessing chronic stress ef....

Protocol

These experiments were conducted in compliance with NIH laboratory animal care guidelines and approved by the Rutgers University Institutional Animal Care and Use Committee.

1. Chronic corticosterone (CORT)

1. Randomly assign mice to treatment groups. Randomly divide adult male C57BL/6J mice into Vehicle and Corticosterone (CORT) groups.
   1. House vehicle mice in distinct cages, and CORT mice in others, as their treatment is delivered via the cage’s water bottle.
   2. Label special water cards to place in the cage that notifies animal care staff that the water bottles contain solutions necessary for the experime....

Results

Chronic CORT was administered for 4 weeks followed by Y-maze barrier training and testing (Figure 1A). In a separate cohort, the 10-day SDS paradigm was similarly followed by training and testing in the Y-maze barrier task (Figure 1C), to determine the effect of these chronic stress paradigms on effort-related choice behavior in male mice. Chronic CORT and SDS both reduced mean body weight compared to Vehicle mice and SDS Control mice as determined by t.......

Discussion

While the chronic CORT paradigm provides a constant CORT dose in the drinking water, from experience there can be some variability in amount consumed by mice. Further, consumption can only be assessed for the total cage, and an average taken based on the number of mice in the cage. Additionally, spillage can occur when weighing the bottles, transferring the mice for behavior testing, or when changing to a fresh cage. However, tracking Vehicle and CORT consumption is still feasible and accurate across weeks of treatment a.......

Materials

Name	Company	Catalog Number	Comments
Acrylic Sheet	McMaster Carr	8560K215	Clear, 3/16" thick, 24" X 36"
Beta-cyclodextrin	Sigma-Aldrich	C4767	500 mg
C57BL/6J Mice	Jackson Labs	000664	Adults age 7-8 weeks
Corticosterone	Sigma-Aldrich	C2505 or C27840	100 or 500 mg
Male CD-1 Mice	Charles River	022	"Retired Breeders"
PVC Acrylic Sheet	McMaster Carr	8560K215	White, 3/16" thick, 48" X 48"
Solidstate Ultrasonic Cleaner	Fisher Scientific	FS-28	Must reach 40 kHz
Steel Wire Cloth	McMaster Carr	9219T143	1 ft X 2 ft