• Floor van Heesch, Jolanda Prins, Gerdien A H Korte-Bouws, Koen G C Westphal, Suzanne Lemstra, Berend Olivier, Aletta D Kraneveld, and S Mechiel Korte.
• Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. F.vanHeesch@uu.nl
• Behav. Brain Res. 2013 Sep 15;253:191-5.

AbstractMany 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.Copyright © 2013 Elsevier B.V. All rights reserved.

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