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Updated: Jul 4, 2026
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Mouse strain differences in the unpredictable chronic mild stress: a four-antidepressant survey
Ipek Yalcin1, Catherine Belzung, Alexandre Surget
1Université François Rabelais de Tours, France.
Abstract:
There have been few comparisons of strains and antidepressants in the unpredictable chronic mild stress (UCMS) paradigm in mice. This study was undertaken to determine the influence of such factors using four antidepressants drugs including the tricyclics imipramine (20 mg/(kgday)) and desipramine (10 mg/(kgday)), the tetracyclic maprotiline (20 mg/(kgday)) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10mg/(kgday)) in both Swiss and BALB/c mice. A 6-week UCMS regimen induced deterioration of the coat state and decreased grooming behaviours in the splash test in BALB/c mice but not Swiss mice. The four antidepressants reversed the UCMS-induced effects in BALB/c mice in both measures. However, imipramine and fluoxetine reached significance in the splash test while desipramine and maprotiline displayed only a trend. In conclusion, these results emphasize that BALB/c mice are more sensitive than Swiss mice for studying the effects of the UCMS model as well as for testing antidepressant-like properties.
Insights
BALB/c mice show increased sensitivity to unpredictable chronic mild stress (UCMS) and antidepressant effects compared to Swiss mice. This highlights BALB/c mice as a better model for UCMS studies and antidepressant drug testing.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- Limited comparative studies exist on antidepressant efficacy within the unpredictable chronic mild stress (UCMS) paradigm across different mouse strains.
- The UCMS model is crucial for investigating depression and evaluating potential antidepressant therapies.
Purpose of the Study:
- To compare the effects of four distinct antidepressants on BALB/c and Swiss mice subjected to the UCMS paradigm.
- To determine the differential sensitivity of mouse strains to UCMS-induced behavioral changes and antidepressant interventions.
Main Methods:
- BALB/c and Swiss mice were exposed to a 6-week unpredictable chronic mild stress (UCMS) regimen.
- Four antidepressants (imipramine, desipramine, maprotiline, fluoxetine) were administered at specific dosages.
- Coat state and grooming behavior in the splash test were assessed to measure stress-induced changes and antidepressant efficacy.
Main Results:
- UCMS induced coat deterioration and reduced grooming in BALB/c mice, but not Swiss mice.
- All four tested antidepressants reversed UCMS-induced effects in BALB/c mice.
- Imipramine and fluoxetine demonstrated significant antidepressant-like effects in the splash test for BALB/c mice.
Conclusions:
- BALB/c mice are more sensitive to the UCMS model than Swiss mice.
- BALB/c mice are a suitable strain for evaluating antidepressant-like properties in preclinical studies.
- The findings provide valuable insights into strain-specific responses in depression modeling and drug discovery.
