Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice

Eur Neuropsychopharmacol. 2011 Jan;21(1):108-16. doi: 10.1016/j.euroneuro.2010.08.005. Epub 2010 Sep 22.

Abstract

Human gene association studies have produced conflicting findings regarding the relationship between the 5-HT transporter (5-HTT) and anxiety. In the present study genetically modified mice were utilised to examine the effects of changes in 5-HTT expression on anxiety. In addition, the influence of 5-HTT expression on two innate "species-typical" behaviours (burrowing and marble burying) and body weight was explored. Across a range of models, 5-HTT overexpressing mice displayed reduced anxiety-like behaviour whilst 5-HTT knockout mice showed increased anxiety-like behaviour, compared to wildtype controls. In tests of species-typical behaviour 5-HTT overexpressing mice showed some facilitation whilst 5-HTT knockout mice were impaired. Reciprocal effects were also seen on body weight, as 5-HTT overexpressors were lighter and 5-HTT knockouts were heavier than wildtype controls. These findings show that variation in 5-HTT gene expression produces robust changes in anxiety and species-typical behaviour. Furthermore, the data add further support to findings that variation of 5-HTT expression in the human population is linked to changes in anxiety-related personality traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / metabolism
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / metabolism
  • Behavior, Animal*
  • Body Weight
  • Female
  • Humans
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin