AbstractThis 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. Curr. Protoc. Neurosci. 54:9.36.1‐9.36.8. © 2011 by John Wiley & Sons, Inc.
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