Chronic Unpredictable Mild Stress Model of Depression: Possible Sources of Poor Reproducibility and Latent Variables

Abstract

Major depressive disorder (MDD) is one of the most common mood disorders worldwide. A lack of understanding of the exact neurobiological mechanisms of depression complicates the search for new effective drugs. Animal models are an important tool in the search for new approaches to the treatment of this disorder. All animal models of depression have certain advantages and disadvantages. We often hear that the main drawback of the chronic unpredictable mild stress (CUMS) model of depression is its poor reproducibility, but rarely does anyone try to find the real causes and sources of such poor reproducibility. Analyzing the articles available in the PubMed database, we tried to identify the factors that may be the sources of the poor reproducibility of CUMS. Among such factors, there may be chronic sleep deprivation, painful stressors, social stress, the difference in sex and age of animals, different stress susceptibility of different animal strains, handling quality, habituation to stressful factors, various combinations of physical and psychological stressors in the CUMS protocol, the influence of olfactory and auditory stimuli on animals, as well as the possible influence of various other factors that are rarely taken into account by researchers. We assume that careful inspection of these factors will increase the reproducibility of the CUMS model between laboratories and allow to make the interpretation of the obtained results and their comparison between laboratories to be more adequate.

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway

“…All experimental mice were weighed every three days. In order to improve the reproducibility of CUMS model, 33 we have taken the following measures: (1) To prevent the effects on mice from experiencing sleep deprivation for a long time, we minimized the experimental time and conducted all behavioral tests from 9:00 AM to 15:00 PM. (2) Since CUMS is effective only if the protocol is implemented in the daytime, all stressors are performed during the daytime, except for the light/dark cycle inversion experiment.…”

Psychological trauma, posttraumatic stress disorder and trauma-related depression: A mini-review

“…There is additional type of trauma called chronic unpredictable mild stress (CUMS), which has been used to model depressive symptoms in rodents[ 12 ]. Long-term (> 3 wk) exposure to a series of mild but unpredictable stressors can make animals depressive, which simulates a depressive state of human beings after encountering the stressors in the real world.…”

Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease

“…The complexity and diversity of chronic stress paradigms challenge the rigor and reproducibility of these models. Behavioral models commonly differ depending on the vivarium facilities, the number of researchers, the available equipment, and the rodent strain used for these studies; however, chronic stress paradigms may be more widely variable due to the types and combinations of stressors, and the duration of the stress protocol [3]. Investigating the inflammatory effect of these chronic stress models, and their relationship to chronic stress in humans, adds a layer of complexity to selecting the are compromised, circulating inflammatory cytokines, specifically IL-1β, TNF-α, and IL-6, may impede tight junction regulation in brain endothelial cells (BECs), thereby impairing BBB integrity and enhancing permeability [25].…”