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

Allan V. Kalueff*, Pamela S. Gallagher, Dennis L. Murphy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1347-1351
Number of pages5
Issue number12
Publication statusPublished - Aug 2006
Externally publishedYes


  • Anhedonia
  • C57BL/6 genetic background
  • Depression
  • Hedonic behavior
  • Knockout mice
  • Serotonin transporter
  • Sucrose preference


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