Are serotonin transporter knockout mice 'depressed'?: hypoactivity but no anhedonia

Neuroreport. 2006 Aug 21;17(12):1347-51. doi: 10.1097/01.wnr.0000230514.08962.76.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Depression / genetics*
  • Depression / physiopathology*
  • Exploratory Behavior / physiology
  • Food Preferences / physiology*
  • Hypokinesia / genetics
  • Hypokinesia / physiopathology*
  • Male
  • Mice
  • Mice, Knockout / physiology*
  • Serotonin Plasma Membrane Transport Proteins / deficiency*
  • Sucrose / administration & dosage


  • Serotonin Plasma Membrane Transport Proteins
  • Sucrose