CUMS Model

Cataglog Number: CG0016

Genetic Background: C57BL/6JCya

Disease Simulated: Depression

Strain Description

Depression is a prevalent psychiatric disorder primarily affecting mood and behavior, characterized by persistent sadness, loss of interest, and anhedonia, often accompanied by fatigue, impaired concentration, and low self-esteem. Additional symptoms include changes in appetite and sleep patterns. Globally, around 264 million people are affected by depression, predominantly within adult and elderly populations ^[1-2].

The Chronic Unpredictable Mild Stress (CUMS) model is currently the most widely used, reliable, and effective rodent model for studying depression ^[3]. In this model, mice are subjected to various mild stressors in an unpredictable sequence over several weeks, including mild electric shocks, food and water deprivation, cage tilting, and wet bedding ^[4-5]. The CUMS model replicates the chronic and unpredictable stress that contributes to depression in humans. Key features of this model include behavioral changes, such as anhedonia, despair, and social withdrawal, which mirror symptoms observed in human depression, as well as neurobiological changes, including disruptions in neurotransmitter systems, neurogenesis, and brain plasticity. This model is valuable for investigating the pathophysiology of depression and evaluating potential antidepressant therapies, offering insights into both the behavioral and neurobiological consequences of chronic stress and depression.

Modeling Protocol

• Model Construction: Male C57bl/6J mice at 4 weeks were subjected to different and repeated unpredictable stressors for five weeks to establish the chronic unpredictable mild stressor (CUMS) model. The CUMS-induced depressed mice were exposed to various mild stressors that changed from day to day to establish an unpredictable procedure. The stressors involved changes in the environment (reversed light/dark cycle, restraint, cage tilting, strobe light, wet bedding), social stressors (crowding), fear stressors (cold swim, tail pinch), and water/food deprivation (as shown in Table 1).
  
  

• Behavioral Assessments: After five weeks of the CUMS procedure, mice received intravenous injections of Fluoxetine (Flu, 600 μg/kg) every three days for two weeks. Following the treatment period, the mice underwent the sucrose preference test, open field test, and forced swim test to assess their depressive-like behavior.

Validation Data

1. Behavior Test

Figure 1. (A) Experimental timeline of the behavior tests, CUMS procedures, and treatment schedules. (B). Behavior tests comprised a sucrose preference test, open field test, and forced swim test at specific time points. The significant differences between groups were analyzed by one-way ANOVA method, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.001.

Behavior Phenotype Summary

• After 7 weeks of the CUMS procedure, the decreased sucrose preference indicated an anhedonic state in the mice. The reduction in the percentage of central time in the open field test reflected increased anxiety, and the longer immobility time in the forced swim test suggested a diminished will to survive.
• Two weeks of fluoxetine administration improved anhedonia, reduced anxiety, and enhanced the survival drive in these mice.

References
[1]Monroe SM, Harkness KL. Major Depression and Its Recurrences: Life Course Matters. Annu Rev Clin Psychol. 2022 May 9;18:329-357.
[2]Rotenstein LS, Ramos MA, Torre M, Segal JB, Peluso MJ, Guille C, Sen S, Mata DA. Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis. JAMA. 2016 Dec 6;316(21):2214-2236.
[3]Hao Y, Ge H, Sun M, Gao Y. Selecting an Appropriate Animal Model of Depression. Int J Mol Sci. 2019 Sep 28;20(19):4827.
[4]Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev. 2019 Apr;99:101-116.
[5]Markov DD, Novosadova EV. Chronic Unpredictable Mild Stress Model of Depression: Possible Sources of Poor Reproducibility and Latent Variables. Biology (Basel). 2022 Nov 6;11(11):1621.