The “depression-related” consequences of rodent 5-HTT knockout mice are, at first blush, less consistent than the anxiety-related consequences, in that they are seen in some of the standard rodent assays for this behavior but not others. This variability may, however, be a legitimate reflection of differences in the level of stress evoked under varying test conditions. In support of this hypothesis, following repeated exposure to stress (e.g., forced swimming, tail suspension), 5-HTT knockout mice develop a depression-related “despair-like” phenotype that is not seen with single exposure (97). The parallels with the primate data showing that the S-allele influence on depression is contingent upon repeated stress exposure are clear.
