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

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ID: 152121
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.
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korte-bouws2018pharmaceuticalsbacterial Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Gerdien A. H. Korte-Bouws;Floor van Heesch;Koen G. C. Westphal;Lisa M. J. Ankersmit;Edwin M. van Oosten;Onur Güntürkün;S. Mechiel Korte
Journal journal of cerebral blood flow and metabolism
Year 2018
DOI
10.3390/ph11030066
URL
http://www.mdpi.com/1424-8247/11/3/66
Keywords
metabolism lipopolysaccharide microdialysis medial prefrontal cortex proinflammatory cytokines

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