Selective breeding for dominant and submissive behavior in Sabra mice

Area of Science:

• Behavioral Neuroscience
• Genetics
• Pharmacology

Background:

• The Dominant-Submissive Relationship (DSR) model is utilized for mood stabilizer and antidepressant drug efficacy testing.
• Antidepressant treatment demonstrably reduces submissive behavior in a dose-dependent manner.
• Clinical studies indicate a genetic component in human depression, prompting investigation into genetic predisposition in animal models.

Purpose of the Study:

• To investigate the genetic basis of submissive behavior using the DSR model.
• To determine if selective breeding can enhance the frequency of DSR formation.
• To validate the DSR test as a model for depression.

Main Methods:

• Selective breeding was applied to outbred Sabra mice based on the DSR paradigm.
• Mice were bred across four generations, pairing individuals selected for dominant traits with those selected for submissive traits.
• The F2 generation was treated with imipramine (10mg/kg) to assess antidepressant effects.

Main Results:

• A gradual increase in the frequency of DSR formation was observed across four generations of selectively bred mice.
• Chronic imipramine administration significantly reduced submissive behavior in the F2 generation.
• These findings were consistent with effects observed in unselected C57BL/6J mice.

Conclusions:

• The increased frequency of DSR formation suggests a significant genetic component for dominant and submissive phenotypes.
• These findings strengthen the predictive and face validity of the DSR test as a model for depression.
• Selective breeding offers a valuable approach to understanding the genetic underpinnings of behaviors relevant to affective disorders.