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.
Highlights
The neurotransmitter 5-hydroxytryptamine (5-HT/serotonin) has been linked to the pathology of a number of psychiatric
The s allele has been associated with a number of outcomes, including anxietyrelated personality traits (Lesch et al, 1996; Du et al, 2000; Greenberg et al, 2000; Melke et al, 2001), mood disorders (Lotrich and Pollock, 2004; Lasky-Su et al, 2005), and suicide (Anguelova et al, 2003; Roy et al, 2007). s allele carriers have been found to display significantly greater amygdala activation to fearful faces (Hariri et al, 2002; Hariri et al, 2005) aversive pictures (Heinz et al, 2005) and negative words (Canli et al, 2005) compared to non-carriers, which may indicate a role for amygdala hyperresponsivity in the observed vulnerabilities
5-HT transporter (5-HTT) KO mice did not differ from wildtypes on the latency to first enter an open arm [F(1,12) = 2.20 p = 0.16]
Summary
The neurotransmitter 5-hydroxytryptamine (5-HT/serotonin) has been linked to the pathology of a number of psychiatric (D.M. Bannerman). 5-HT is removed from the synapse primarily by the 5-HT transporter (5-HTT), which is instrumental in regulating 5HT activity (Bradley and Blakely, 1997). The s allele has been associated with a number of outcomes, including anxietyrelated personality traits (Lesch et al, 1996; Du et al, 2000; Greenberg et al, 2000; Melke et al, 2001), mood disorders (Lotrich and Pollock, 2004; Lasky-Su et al, 2005), and suicide (Anguelova et al, 2003; Roy et al, 2007). S allele carriers appear to be more sensitive to stressful life events (Caspi et al, 2003; Pluess et al, 2010)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
