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A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits
Published on: November 24, 2015
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Mouse Model of Chronic Social Stress-Induced Excessive Pavlovian Aversion Learning-Memory.
Hannes Sigrist1, David E Hogg1, Alena Senn1
1Preclinical Laboratory, Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry and University of Zurich, Zurich, Switzerland.
Current Protocols
|March 11, 2024
Summary
Chronic social stress in mice increases aversion learning and memory, leading to hypersensitivity to negative stimuli. This preclinical model accurately predicts treatments for aversion hypersensitivity in humans.
Area of Science:
- Neuroscience
- Behavioral Science
- Psychiatry
Background:
- Increased sensitivity to aversive stimuli is a key feature in psychiatric disorders like anxiety, PTSD, and depression.
- Chronic stress is a significant risk factor and symptom, manifesting as heightened perception and reactivity to negative events.
- Pavlovian aversion learning and memory (PAL, PAM) in rodents, measured by freezing behavior, is a well-established model for studying aversion.
Purpose of the Study:
- To establish and validate a mouse model of chronic social stress (CSS) that mimics human exposure to sustained threat.
- To investigate the effects of CSS on Pavlovian aversion learning and memory (PALM).
- To assess the utility of this model for preclinical testing of compounds aimed at normalizing aversion hypersensitivity.
Main Methods:
- The chronic social stress (CSS) model involves exposing adult male mice to dominant aggressors for 15 days, with controlled daily attacks.
- Pavlovian aversion learning and memory (PALM) was assessed by measuring freezing behavior in response to conditioned stimuli (tone) and unconditioned stimuli (foot shock).
- Control mice were housed in standard pairs, and behavioral testing involved comparing CSS mice with control (CON) mice.
Main Results:
- Mice subjected to CSS exhibited significantly higher levels of freezing during both learning and memory phases of PALM compared to control mice.
- This indicates that CSS leads to a generalized hypersensitivity to aversive stimuli, increasing the salience of negative events.
- The model demonstrated high reproducibility, minimal wounding, male specificity, and absence of distinct susceptible/resilient subgroups.
Conclusions:
- Chronic social stress induces a state of generalized aversion hypersensitivity in male mice, as evidenced by enhanced Pavlovian aversion learning and memory.
- This CSS model provides a robust and reproducible platform for preclinical research in psychiatry, particularly for studying stress-related disorders.
- The model shows promise for accurately predicting the efficacy of novel therapeutic compounds in normalizing aversion hypersensitivity relevant to human patients.
