Systemic tumor necrosis factor-alpha decreases brain stimulation reward and increases metabolites of serotonin and dopamine in the nucleus accumbens of mice
•Peripherally injected TNF-alpha induces anhedonia in mice.•Accumbal extracellular 5-HIAA levels increase in response to peripheral TNF-alpha.•Accumbal extracellular HVA levels increase in response to peripheral TNF-alpha. Many patients with chronic inflammatory disorders have an abnormal high preva...
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Veröffentlicht in: | Behavioural brain research 2013-09, Vol.253, p.191-195 |
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Sprache: | eng |
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Zusammenfassung: | •Peripherally injected TNF-alpha induces anhedonia in mice.•Accumbal extracellular 5-HIAA levels increase in response to peripheral TNF-alpha.•Accumbal extracellular HVA levels increase in response to peripheral TNF-alpha.
Many patients with chronic inflammatory disorders have an abnormal high prevalence of major depression accompanied by elevated levels of tumor necrosis factor-α (TNF-α). We hypothesize that systemic TNF-α increases brain monoamine metabolism, which might induce anhedonia (i.e. a core symptom of major depression). The effect of an intraperitoneal TNF-α injection on extracellular monoamine and metabolite concentrations was investigated by in vivo microdialysis in the nucleus accumbens (NAc) of C57BL/6 mice. In another group, the effects of TNF-α on body weight and intracranial self-stimulation (ICSS) thresholds were measured. TNF-α reduced body weight and increased ICSS thresholds, suggesting a state of anhedonia. TNF-α did not affect serotonin levels, but increased its metabolite 5-HIAA in the NAc. Remarkably, TNF-α also increased the dopamine metabolite HVA, without affecting dopamine levels itself. These data concur with earlier findings that pro-inflammatory cytokines enhance serotonin transporter activity, and possibly also dopamine transporter activity in the brain. However, more research is needed to understand the precise molecular mechanisms by which TNF-α increases transporter activity and anhedonia. |
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ISSN: | 0166-4328 1872-7549 |
DOI: | 10.1016/j.bbr.2013.07.038 |