Reduction of Submissive Behavior Model for Antidepressant Drug Testing in Mice

Dominant submissive relationship (DSR)-based models, one for antidepressant testing, the reduction of submissive behavior model (RSBM), and another for antimanic drug testing, the reduction of dominant behavior model (RDBM), were first established in rats. This chapter discusses development of the RSBM in mice. Mouse strains involved in this task were the inbred strains C57BL/6 J and Balb/c and the outbred SABRA mouse. The predictive validity of the RSBM was studied for the C57BL/6 J mouse by testing several antidepressants (desipramine, imipramine, amitriptyline, fluoxetine, amoxapine) and non-antidepressants (amphetamine, yohimbine, thiotixen and diazepam) for reduction submissive mouse behavior as determined in a competition for palatable food test. The face validity was studied for the SABRA mouse by determining if there is a genetic component for dominant and submissive traits. Technical details of the RSBM and data analysis that need to be considered for successful application of this methodology in research are also discussed.