Antidepressant Drug Studies in Mice

The chronic social defeat stress paradigm induces depression by repeatedly exposing naïve mice to aggressor mice. After 15 days in this emotionally stressful environment, mice display robust depressive phenotypes, which are characteristic of human symptoms. The hallmark behaviors of this model include anhedonia, anxiety and social-avoidance behavior as measured by:

  • Reduced activity in an open field
  • Reduced number of rears
  • Increased immobility
  • Impaired performance in a long-term memory test (contextual fear conditioning)
  • Impaired performance in active avoidance test

Collectively, these endpoints provide a comprehensive model of depression to assess the efficacy of your antidepression therapy candidates. This flexible study paradigm allows either chronic or acute antidepressant treatments, as well as client-specified dosing programs, translating to better predictive value for your drug candidate’s intended use.

  • ANTIDEPRESSANT DRUG STUDY PARADIGM

     

    Outline of antidepressant drug study using chronic social defeat stress model paradigm

    Example of the chronic social defeat study paradigm. Treatment regimen is study-dependent.

  • DEPRESSION MODEL VALIDATION DATA
    chart of open field distant traveled and vertical rearings in chronic social defeat and control mice

    Chronic Social Defeat (CSD) mice are less active and demonstrate a reduction in rearing relative to control mice.

    charts of open field resting %, distance traveled in center, and average velocoity in chronic social defeat and control mice

    CSD mice spend more time immobile in the open field than control mice (A). CSD mice spend less time in the center of the open field (B), which suggests heightened anxiety. Mobile CSD mice move at the same velocity as control mice (C), suggesting no motor impairment.

     

    line graph of contextual fear conditioning test in chronic social defeat and control mice

    CSD mice displayed impaired acquisition in a contextual fear conditioning paradigm.

     

    bar graph of active avoidance in chronic social defeat and control mice

    When tested in an active avoidance paradigm, CSD mice had a significant reduction in the number of active avoidances and a significant increase in no-response trials.

     

    chart of sucrose preference test results in chronic social defeat and control mice

    When tested in a sucrose preference test, CSD mice had a reduced preference for sucrose (relative to water) as compared to control mice.