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Oxford, United Kingdom

Couch Y.,Mansfield Road | Xie Q.,Mansfield Road | Lundberg L.,Mansfield Road | Lundberg L.,Public Health England | And 2 more authors.
PLoS ONE | Year: 2015

It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours postinjection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS. © 2015 Couch et al. Source

Line S.J.,South Parks Road | Barkus C.,South Parks Road | Coyle C.,South Parks Road | Jennings K.A.,Mansfield Road | And 4 more authors.
European Neuropsychopharmacology | Year: 2011

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. © 2010 Elsevier B.V. and ECNP. Source

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