| A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. | |
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MedLine Citation:
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PMID: 22251606 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRI; SNRI) are the first choice pharmacological treatment options for major depression. It has long been assumed that the primary therapeutic mechanism of action of these drugs involves the modulation of monoaminergic systems. However, contemporary investigations have revealed that depression is linked with inflammation, and that SSRI/SNRIs possess significant anti-inflammatory actions. While these anti-inflammatory properties initially only related to work undertaken on cells of the peripheral immune system, it has recently become apparent that these drugs also exert anti-inflammatory effects on microglia, the principal cells within the CNS that regulate and respond to inflammatory factors. The aim of the current study was to compare SSRI/SNRIs in terms of their anti-inflammatory potency, and to determine the specific mechanisms through which these effects are mediated. Accordingly, the current study evaluated the ability of five different SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) and one SNRI (venlafaxine) to suppress microglial responses to an inflammatory stimulus. Specifically, we examined their ability to alter tumour necrosis factor-α (TNF-α) and nitric oxide (NO) production after 4 and 24h stimulation with lipopolysaccharide. Our results indicated that the SSRIs potently inhibited microglial TNF-α and NO production. We then investigated whether these effects might involve either β-adrenoceptor or cAMP signalling. Using the protein kinase A inhibitor Rp-CAMPs, we found evidence to suggest that cAMP signalling is involved in regulating the anti-inflammatory response. These findings suggest that antidepressants may owe at least some of their therapeutic effectiveness to their anti-inflammatory properties. |
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Authors:
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Ross J Tynan; Judith Weidenhofer; Madeleine Hinwood; Murray J Cairns; Trevor A Day; Frederick R Walker |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-11 |
Journal Detail:
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Title: Brain, behavior, and immunity Volume: - ISSN: 1090-2139 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8800478 Medline TA: Brain Behav Immun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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School of Biomedical Sciences & Pharmacy, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Centre for Brain & Mental Health Research, University of Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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