A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Summary

Here, methods for developing a mouse model of subchronic and mild social defeat stress are described and used to investigate the pathogenic features of depression including hyperphagia- and polydipsia-like symptoms following increased body weight.

Abstract

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of depression is essential. Because there are several types of depression, various animal models are needed for a deeper understanding of the disorder. Previously, a mouse model of subchronic and mild social defeat stress (sCSDS) using a modified chronic social defeat stress (CSDS) paradigm was established. In the paradigm, to reduce physical injuries from aggressors, the duration of physical contact between the aggressor and a subordinate was reduced compared to in the original CSDS paradigm. sCSDS mice showed increased body weight gain, food intake, and water intake during the stress period, and their social behaviors were suppressed after the stress period. In terms of the face validity of the stress-induced overeating and overdrinking following the increased body weight gain, the sCSDS mice may show some features related to atypical depression in humans. Thus, a mouse model of sCSDS may be useful for studying the pathogenic mechanisms underlying depression. This protocol will help establish the sCSDS mouse model, especially for studying the mechanisms underlying stress-induced weight gain and polydipsia- and hyperphagia-like symptoms.

Introduction

Many kinds of stressful events occur throughout the lives of humans. Excessive stress often leads to harmful physiological consequences in humans and animals. In humans, stressful events are major risk factors for precipitating psychiatric disorders such as depression¹. A Global Burden of Disease study indicated that depression is one of the most disabling disorders in terms of disability-adjusted life years (DALYs) and years lived with disability². In addition, depression accounts for the largest proportion of suicide DALYs³. People suffering from depression find it difficult to manage their lives, and as a result, their quality of li....

Protocol

The animal studies were approved by and met the guidelines of both the Animal Care and Use Committee of Ibaraki University and the Ministry of Education Culture, Sports, Science, and Technology (MEXT), Japan (Notification No.71). A complete overview of the protocol is shown in Figure 1.

1. Apparatus

1. Prepare two kinds of cages: a single cage (width [W] × depth [D] × height [H] = 143 mm × 293 mm × 148 mm), and a “social defeat (SD)” cage (W × D × H = 220 mm × 320 mm × 135 mm).
2. As shown in Figure 2, divide the SD cage into two compartmen....

Results

To monitor the degree of physical stress for over the 10-day periods, the number of attack bites by ICR mice was manually counted by a researcher. Figure 5A indicates the individual values for the number of attack bites received. There was considerable variability in the early stage (approximately 10–120 bites on day 1), but this variability was reduced in the later stage (approximately 5–20 bites on day 10). Figure 5B indicates that the average number of attack bites received gradually .......

Discussion

There were definitive differences in body weight between sCSDS mice and CSDS mice subjected to the standard CSDS protocol (5 to 10 min of physical contact with aggressors per day)¹⁹. The sCSDS mice showed increased BWG during the stress period, whereas the standard CSDS mice showed a decrease in body weight during the stress period^21,22,23. There is a substantial difference between the two protocols in terms of the total duration of physical contact with aggressors during the 10-day stress period. W.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
single cage	Charles River Laboratories Japan		width [W] × depth [D] × height [H] = 143 × 293 × 148 mm
M cage	Natsume Seisakusho		W × D × H = 220 × 320 × 135 mm
Whiteflake	Charles River Laboratories Japan		Wood-shaving chips made from spruce trees
AIN-93G	Oriental Yeast		purified-diet food pellets
Kimtowel	Nippon Paper Crecia Co.		Paper towels
open-field arena	O’Hara & Co.		made of gray polyvinylchloride