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Pharmaceuticals 2018, 11(3), 66; https://doi.org/10.3390/ph11030066

Bacterial Lipopolysaccharide Increases Serotonin Metabolism in Both Medial Prefrontal Cortex and Nucleus Accumbens in Male Wild Type Rats, but Not in Serotonin Transporter Knockout Rats

1
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
2
Department of Biopsychology, Faculty of Psychology, Ruhr-Universität Bochum, Universitätsstraße 150, D-44780 Bochum, Germany
*
Author to whom correspondence should be addressed.
Received: 11 June 2018 / Revised: 29 June 2018 / Accepted: 2 July 2018 / Published: 5 July 2018
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Abstract

It is well known that bacterial lipopolysaccharides (LPS) both increases proinflammatory cytokines and produces sickness behavior, including fatigue and anhedonia (i.e., the inability to experience pleasure). Previously, we have shown that intraperitoneally (i.p.) administered LPS increased extracellular monoamine metabolite levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), which was completely, or at least partly, prevented by pretreatment with a triple reuptake inhibitor that also blocks the serotonin (5-HT) transporter (SERT). This suggests indirectly, that LPS may enhance SERT transporter activity, and consequently, increase removal of 5-HT from the synaptic cleft, and increase metabolism of 5-HT. In the present study, we focus more specifically on the role of SERT in this increased metabolism by using rats, that differ in SERT expression. Therefore, the effects of an intraperitoneal LPS injection on extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were investigated by in vivo microdialysis in the NAc and mPFC of wild type (SERT+/+), heterozygous (SERT+/−) and knockout (SERT−/−) rats. Here, we show that LPS-induced 5-HIAA formation in male rats, is significantly increased in SERT+/+ rats in both the NAc and mPFC, whereas this increase is partly or totally abolished in SERT+/− and SERT−/− rats, respectively. Thus, the present study supports the hypothesis that systemic LPS in male rats increases SERT function and consequently enhances 5-HT uptake and metabolism in both the NAc and mPFC. View Full-Text
Keywords: lipopolysaccharide; proinflammatory cytokines; serotonin transporter; Slc6a41; metabolism; microdialysis; medial prefrontal cortex; nucleus accumbens lipopolysaccharide; proinflammatory cytokines; serotonin transporter; Slc6a41; metabolism; microdialysis; medial prefrontal cortex; nucleus accumbens
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Korte-Bouws, G.A.H.; van Heesch, F.; Westphal, K.G.C.; Ankersmit, L.M.J.; van Oosten, E.M.; Güntürkün, O.; Korte, S.M. Bacterial Lipopolysaccharide Increases Serotonin Metabolism in Both Medial Prefrontal Cortex and Nucleus Accumbens in Male Wild Type Rats, but Not in Serotonin Transporter Knockout Rats. Pharmaceuticals 2018, 11, 66.

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