A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice

• Published in: PloS one 2015-07, Vol.10 (7), p.e0130643-e0130643
• Main Authors: Couch, Yvonne, Xie, Qin, Lundberg, Louise, Sharp, Trevor, Anthony, Daniel C
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Behavior; Binding sites; Brain; Central nervous system; Chronic fatigue syndrome; Cytokines; Disease Models, Animal; Endotoxins; Enzymatic activity; Enzyme activity; Fatigue; Fatigue - etiology; Gene expression; Geographical variations; Infection - complications; Infections; Inflammation; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Male; Mental depression; Mice; Moods; mRNA; Pharmacology; Psychiatry; Receptor, Serotonin, 5-HT2A - metabolism; Rodents; Serotonin; Serotonin S2 receptors; Sucrose; Sugar; TNF inhibitors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130643

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.