Abstract
This protocol describes a simplified method for inducing a chronic depression-like state in mice that is based on the repeated open-space forced swim method originally developed for rats. The method consists of mice swimming daily in lukewarm water in rat tub cages, for 15 min/day for 4 days, and thereafter once per week. This procedure produces a progressive decrease in distance swum and a concomitant increase in immobility (floating) in ∼70% of the mice, both of which persist unaltered for weeks. The model has predictive, face, and construct validity and has a number of advantages over previous methods in that it utilizes very mild stress, is short in duration, and is easily standardized. Moreover, since it utilizes a greater swimming area than the traditional (Porsolt) method it can be used to study interactions of depressive behavior with behavioral flexibility and perseveration.