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Disease Models | Common Chronic Stress Animal Models: CUMS, CSDS, CRS, and SIS—How to Tell Them Apart?

 

Depression is a common psychiatric disorder whose principal clinical features include anhedonia, diminished motivation, cognitive deficits, and depressed mood. Genetic factors account for approximately 40% of depressive cases, with the remainder attributable to environmental influences. Chronic stress responses triggered by environmental risk factors can mediate the development of depression. To better elucidate the pathophysiological mechanisms of depression and to identify therapeutic strategies, it is essential to establish an effective animal model of depression.

 

Common animal models of chronic stress

 

Common animal models of chronic stress include the chronic social defeat stress (CSDS) model, the chronic restraint stress (CRS) model, the chronic unpredictable mild stress (CUMS) model, and the chronic social isolation stress (SIS) model.

 

| Chronic Unpredictable Mild Stress (CUMS) Model

 

The CUMS model has become the most widely used animal model for studying depression and is extensively employed in preclinical antidepressant screening.

 

Aniphe BioLab Case Study:

 

| Laboratory Animals

 

C57 male, 6–8 weeks old.

 

| Modeling Method

 

The experimental stimuli were as follows:

 

1-hour foot shock (all at 1 mA, lasting 1–10 seconds, on average once per minute), 24-hour food deprivation, swimming in 4°C cold water for 5 minutes, 24-hour water deprivation, reversed day–night cycle, wet bedding for 24 hours, 24-hour absence of bedding, tail clamping for 5 minutes, restraint for 6 hours, and noise exposure for 1 hour.

Image source: Aniphe BioLab

Stress stimulation protocol for the model group:

 

The model was constructed over six weeks, with a random combination of any two stressors each day; no two consecutive days were allowed to feature the same stressor, ensuring the unpredictability of the stressors.

 

| Evaluation Method

 

01 Status Monitoring: During the model‑establishment process, record the mice’s behavior and body weight.

02 Sucrose Preference Test: Calculate the sucrose preference percentage for each mouse [Preference = (sucrose intake / total liquid intake) × 100%].

03 Open-field test and forced swim test: The open-field test and the forced swim test were conducted in the sixth week after model induction.

 

| Experimental Results

 

 

 

A: Body weight, B: Preference for sugary water, C: Forced swim test, D: Open-field test; image source: Aniphe BioLab.

 

As shown in the figure, compared with the control group, the CUMS‑treated group exhibited a significant reduction in body weight, with a highly significant difference (P < 0.001). Sucrose solution intake was markedly decreased, reaching statistical significance (P < 0.05). In the open‑field test, the distance traveled was reduced. The number of swimming bouts was significantly lower, with a highly significant difference (P < 0.001).

 

By observing changes in animal behavior, it is possible to evaluate the efficacy of antidepressant drugs and investigate the etiology of depression. The currently accepted approach involves symptom‑based and behavioral assays. Other behavioral methods, along with their respective advantages and disadvantages, are summarized in Table ↓.

 

 

Image source: Aniphe BioLab

 

| Other Common Animal Models of Chronic Stress

 

① Chronic Social Defeat Stress Model (CSDS)

 

The core principle of the CSDS model is to induce depression-like behaviors in experimental animals by subjecting them to repeated social defeat stress. Specifically, this procedure involves housing an experimental animal together with an aggressive conspecific—typically a screened male mouse or rat. The aggressive animal repeatedly and aggressively attacks the experimental animal, thereby exposing it to sustained social defeat.

 

② Chronic restraint stress model CRS

 

The CRS model is a prototypical paradigm for eliciting nonspecific stress responses and is widely employed in research on stress‑related psychiatric disorders. Commonly used restraint devices include perforated centrifuge tubes, conical tubes, and small‑animal restrainers, with the aim of inducing physiological stress responses by limiting the animals’ freedom of movement.

 

③ Chronic Social Isolation Stress Model SIS

 

The SIS model is designed to simulate conditions in which humans lack social interaction and support within a social environment. The SIS modeling process can be divided into two approaches: one involves isolating experimental animals immediately after weaning, and the other entails isolation beginning in adulthood. The SIS model enables the exclusion of social interactions among conspecifics.

The advantages and disadvantages of common animal models of chronic stress are summarized in the following table:

 

 

Image source: Aniphe BioLab

 

Summary

 

Selecting an appropriate model is of great significance for investigating the pathogenesis of depression and for drug screening. Aniphe BioLab offers a variety of approaches to establish animal models of depression and provides pharmacological and efficacy evaluation services tailored to these disease models. We welcome all clients to contact us for more information!

 

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