p38 MAP kinase activation does not stimulate serotonin transport in rat brain: Implications for sickness behaviour mechanisms

Filippo Andreetta, Nicholas M Barnes, Paul B Wren, Lucia Carboni

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)


    AIMS: Several studies suggested an association between dysregulation of immune mediators and behavioural, neuroendocrine and neurochemical features of depression. Available data showed that cytokines affect the serotonin transporter (SERT) activity through p38 MAP kinase (MAPK)-dependent mechanisms in some cell lines and mice neurons (Zhu et al., Neuropsychopharmacology, 2006; 31:2121-31). The aim of this study was to investigate the interaction of Interleukin-1β (IL-1β) or p38 MAPK with SERT activity in rat brain and cell lines.

    MAIN METHODS: Synaptosomes or cells were treated with IL-1β or the p38 MAPK activator anisomycin at different concentrations and end-points and the modulation of SERT activity as Km and Vmax was evaluated.

    KEY FINDINGS: Treatments with IL-1β or anisomycin did not affect serotonin uptake and p38 MAPK activation in rat synaptosomes, in contrast to reports in mice (Zhu et al., Neuropsychopharmacology, 2010; 35:2510-20). The same treatments activated p38 MAPK phosphorylation in HeLa cells used as positive controls. Similarly, no changes after anisomycin treatment could be detected in [(3)H]serotonin uptake rate in LLC-PK cells expressing human SERT, although phosphorylated p38 MAPK levels augmented significantly. Direct cytokine release in brain was induced by intracerebroventricular administration of bacterial lipopolysaccaride. Although pro-inflammatory cytokines, such as IL-1ß, IL6, and Tumor Necrosis Factor α, showed significant increases in brain cortex, modulation of SERT activity in term of Km and Vmax was not detected.

    SIGNIFICANCE: These results imply that the stimulation of serotonin uptake by cytokines may not be a unique and fundamental mechanism in the pathology of depression induced by altered immune response.

    Original languageEnglish
    Pages (from-to)30-7
    Number of pages8
    JournalLife Sciences
    Issue number1
    Publication statusPublished - 19 Jul 2013

    Bibliographical note

    Copyright © 2013 Elsevier Inc. All rights reserved.


    • Analysis of Variance
    • Animals
    • Anisomycin
    • Biological Transport
    • Brain
    • Cytokines
    • Depression
    • Enzyme Activation
    • Enzyme-Linked Immunosorbent Assay
    • HeLa Cells
    • Humans
    • Illness Behavior
    • Interleukin-1beta
    • Least-Squares Analysis
    • Male
    • Rats
    • Rats, Sprague-Dawley
    • Serotonin
    • Synaptosomes
    • p38 Mitogen-Activated Protein Kinases


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