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Updated: Mar 7, 2026
Animal Models of Depression - Chronic Despair Model CDM
Published on: September 23, 2021
Modelling depression in animals: at the interface of reward and stress pathways
1Laboratory of Translational Psychiatry, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Heinrich-Hoffmann-Str. 10, 60528, Frankfurt, Germany. david.slattery@kgu.de.
Rationale:
Despite substantial research efforts the aetiology of major depressive disorder (MDD) remains poorly understood, which is due in part to the heterogeneity of the disorder and the complexity of designing appropriate animal models. However, in the last few decades, a focus on the development of novel stress-based paradigms and a focus on using hedonic/anhedonic behaviour have led to renewed optimism in the use of animal models to assess aspects of MDD.
Objectives:
Therefore, in this review article, dedicated to Athina Markou, we summarise the use of stress-based animal models for studying MDD in rodents and how reward-related readouts can be used to validate/assess the model and/or treatment.
Results:
We reveal the use and limitations of chronic stress paradigms, which we split into non-social (i.e. chronic mild stress), social (i.e. chronic social defeat) and drug-withdrawal paradigms for studying MDD and detail numerous reward-related readouts that are employed in preclinical research. Finally, we finish with a section regarding important factors to consider when using animal models.
Conclusions:
One of the most consistent findings following chronic stress exposure in rodents is a disruption of the brain reward system, which can be easily assessed using sucrose, social interaction, food, drug of abuse or intracranial self-stimulation as a readout. Probing the underlying causes of such alterations is providing a greater understanding of the potential systems and processes that are disrupted in MDD.
Insights
This review explores stress-based animal models for major depressive disorder (MDD). Reward-related readouts help validate these models and treatments by assessing disruptions in the brain
Area of Science:
- Neuroscience
- Animal Behavior
- Pharmacology
Background:
- The exact causes of major depressive disorder (MDD) are unclear due to its complexity and the limitations of current animal models.
- Recent advances in stress-based paradigms and the study of hedonic/anhedonic behaviors offer new avenues for MDD research in animals.
Purpose of the Study:
- To review the application of stress-based animal models for studying major depressive disorder (MDD) in rodents.
- To examine how reward-related behaviors can be used to validate these models and potential treatments for MDD.
Main Methods:
- Analysis of chronic stress paradigms, including non-social (chronic mild stress), social (chronic social defeat), and drug-withdrawal models.
- Detailed review of various reward-related readouts used in preclinical research, such as sucrose preference and social interaction tests.
Main Results:
- Chronic stress in rodents consistently disrupts the brain's reward system, impacting behaviors like sucrose consumption and social interaction.
- Reward system alterations in animal models provide insights into the neurobiological underpinnings of MDD.
Conclusions:
- Stress-based animal models, particularly those incorporating reward system assessments, are valuable tools for understanding MDD.
- Further research into these models can elucidate the specific systems and processes implicated in major depressive disorder.
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