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Related Experiment Video

Updated: Mar 23, 2026

The Forced Swim Test as a Model of Depressive-like Behavior
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Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism.

E R de Kloet1, M L Molendijk2

  • 1Division of Medical Pharmacology and Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands; Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.

Neural Plasticity
|April 2, 2016
PubMed
Summary
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The forced swim test (FST) reveals rodent stress coping mechanisms, not depression. Immobility in FST reflects adaptation, not a depression-like phenotype, offering insights into stress response regulation.

Area of Science:

  • Neuroscience
  • Behavioral Science
  • Endocrinology

Background:

  • The forced swim test (FST) is widely used to model depression in rodents, with immobility interpreted as a depression-like state.
  • Recent literature increasingly labels stress-induced immobility in FST as a depression-like phenotype, despite its adaptive role.
  • Understanding the neurobiological underpinnings of stress coping in FST is crucial for accurate interpretation.

Purpose of the Study:

  • To examine information processing during stress coping in the FST.
  • To investigate the role of corticosterone, mineralocorticoid receptors (MR), and glucocorticoid receptors (GR) in regulating active vs. passive coping styles.
  • To propose a model for how the brain regulates behavioral responses to acute stressors.

Main Methods:

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Last Updated: Mar 23, 2026

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The Mouse Forced Swim Test
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  • Analysis of PubMed literature on FST and stress-related immobility.
  • Focus on the action of corticosterone mediated by MR and GR in the limbic brain.
  • Development of a model integrating limbic MR and dopaminergic pathways in regulating coping strategies.

    • Main Results:

    • The FST does not accurately reflect depression but rather adaptive stress coping.
    • Limbic MR-mediated response selection complements dopaminergic executive functions in regulating active/passive coping.
    • Hippocampal GR-dependent action in the dentate gyrus stores preferred coping styles in memory upon stressor removal.

    Conclusions:

    • Rodent immobility in FST signifies adaptive stress coping, not depression.
    • The FST is a valuable paradigm for studying the mechanisms of stress adaptation.
    • Corticosterone, MR, GR, and dopaminergic systems interact to regulate behavioral responses to stressors.