title: A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice.
abstract: 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, 0.5 mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours post-injection 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.
authors.affiliation: Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Couch
authors.affiliation: Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom; Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxford OX11 0RQ, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Lundberg
authors.affiliation: Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom.
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
authors.affiliation: Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, United Kingdom.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005221:Fatigue / Q000209:etiology*; D007239:Infections / Q000150:complications*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D044402:Receptor, Serotonin, 5-HT2A; D014409:Tumor Necrosis Factor-alpha