ReviewPsychopharmacology2022
Chronic mild stress paradigm as a rat model of depression: facts, artifacts, and future perspectives.
Review in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Voluntary wheel-running exercise improvement of anxiety or depressive symptoms in different models of depression.Frontiers in behavioral neuroscience · 2024Pooled it
- Vitamin D binding protein in ventral CA3 of the hippocampus drives stress-induced depression.Science advances · 2026Article
- Engineering a chitosan-based nanoemulsion for non-invasive CNS-targeting approach: dual neuroprotection against epileptic and depressive disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Alamandine attenuates stress-induced inflammation, oxidative stress, and intestinal histopathological alterations in a chronic unpredictable mild stress model of depression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dihydromyricetin attenuates chronic stress-induced depressive-like phenotypes and modulates Akt/FoxO3a-related signaling in the hippocampus.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Psycho-cardiovascular interaction network in cardiovascular health and disease: signaling pathways and molecular mechanisms.Precision clinical medicine · 2026Review
- Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression.Biomolecules · 2026Review
- Development and characterization of a reserpine-induced mouse model of depression: An integrated in-vivo and in-silico approach.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Aerobic Endurance Training Modulates Cardiac Renin-Angiotensin System Peptides and Matrix Metalloproteinase Activity During Chronic Stress.Journal of cellular and molecular medicine · 2026Article
- Comparative analysis of multiple chronic unpredictable mild stress paradigms in mice: Behavioural and physiological validity.Neurobiology of stress · 2026Article
- Neuroimaging insights from Wistar-Kyoto rats under chronic mild stress: morphological and metabolic brain correlates of treatment-resistant depression.Scientific reports · 2026Article
- Maternal immune activation with high molecular weight poly (I:C) induces selective depressive-like phenotype in adult offspring.Translational psychiatry · 2026Article
- Transcranial Photobiomodulation Modulates Oxidative Stress Biomarkers and Complex IV Activity in Anhedonic-Like Behavior.Neurochemical research · 2026Article
- Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.Translational psychiatry · 2026Article
- New Antidepressant Development in the Treatment of Depression.Advances in experimental medicine and biology · 2026Review
- Stable rat models in constipation with depression and anxiety: evaluation and validation.Frontiers in behavioral neuroscience · 2026Article
- Multisystem pathology in chronic variable stress: gut-liver-brain axis disruption and the therapeutic promise of magnesium-L-theanine.Therapeutic advances in endocrinology and metabolism · 2026Review
- Lost in translation: toward clinically effective translational research.Translational psychiatry · 2025Review
- Early maternal separation potentiates the impact of later social isolation in inducing depressive-like behavior via oxidative stress in adult rats.Psychopharmacology · 2025Article
- Rodent chronic variable stress procedures: A disjunction between stress entity and impact on behaviour.Journal of neuroendocrinology · 2025Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
rationaleThe chronic mild stress (CMS) paradigm was first described almost 40 years ago and has become a widely used model in the search for antidepressant drugs for major depression disorder (MDD). It has resulted in the publication of almost 1700 studies in rats alone. Under the original CMS procedure, the expression of an anhedonic response, a key symptom of depression, was seen as an essential feature of both the model and a depressive state. The prolonged exposure of rodents to unpredictable/uncontrollable mild stressors leads to a reduction in the intake of palatable liquids, behavioral despair, locomotor inhibition, anxiety-like changes, and vegetative (somatic) abnormalities. Many of the CMS studies do not report these patterns of behaviors, and they often fail to include consistent molecular, neuroanatomical, and physiological phenotypes of CMS-exposed animals.
objectivesTo critically review the CMS studies in rats so that conceptual and methodological flaws can be avoided in future studies.
resultsAnalysis of the literature supports the validity of the CMS model and its impact on the field. However, further improvements could be achieved by (i) the stratification of animals into 'resilient' and 'susceptible' cohorts within the CMS animals, (ii) the use of more refined protocols in the sucrose test to mitigate physiological and physical artifacts, and (iii) the systematic evaluation of the non-specific effects of CMS and implementation of appropriate adjustments within the behavioral tests.
conclusionsWe propose methodological revisions and the use of more advanced behavioral tests to refine the rat CMS paradigm, which offers a valuable tool for developing new antidepressant medications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.