Are serotonin transporter knockout mice 'depressed'? Hypoactivity but no anhedonia

Although the serotonin transporter is a key target for antidepressants, its exact role in depression etiology remains unclear. While serotonin transporter knockout mice are a potential model to examine this problem, their depression profile is unclear in several 'despair' tests, and may be confounded by their hypoactivity phenotype (confirmed here by marble-burying and bedding tests). To assess depression in these mice, we evaluated wild-type, heterozygous, and serotonin transporter knockout C57BL/6 male mice on a well-validated, anhedonia-based depression paradigm, the sucrose preference test. Overall, all three genotypes showed similar sucrose preference, indicating an unaltered hedonic state. These results demonstrate that depression-like behavior (unlike hypoactivity) is not a baseline phenotypic feature of serotonin transporter knockout mice, suggesting anew that these mice do not represent a genetic model of depression.