Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter knockout rats: an intracranial self-stimulation study.
Brain, Behavior, and Immunity. 2013-03-01; 29: 98-103
DOI: 10.1016/j.bbi.2012.12.013
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1. Brain Behav Immun. 2013 Mar;29:98-103. doi: 10.1016/j.bbi.2012.12.013. Epub 2012
Dec 28.
Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter
knockout rats: an intracranial self-stimulation study.
van Heesch F(1), Prins J, Konsman JP, Westphal KG, Olivier B, Kraneveld AD, Korte
SM.
Author information:
(1)Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences,
Utrecht University, Faculty of Science, Universiteitsweg 99, Utrecht, The
Netherlands.
A growing body of evidence suggests that pro-inflammatory cytokines contribute to
the pathogenesis of depression. Previously, it has been shown that cytokines
(e.g. interferon-α therapy) induce major depression in humans. In addition,
administration of the cytokine-inducer lipopolysaccharide (LPS) provokes
anhedonia (i.e. the inability to experience pleasure) in rodents. Furthermore,
serum pro-inflammatory cytokine levels are increased in depressed patients.
Nevertheless, the etiology of cytokine-induced depression is largely unknown.
Previously, it has been shown that selective serotonin re-uptake inhibitors
decrease serum pro-inflammatory cytokine levels and that pro-inflammatory
cytokines increase activity of the serotonin transporter (SERT). The purpose of
this study was to explore the effect of partial and complete lack of the SERT in
LPS-induced anhedonia assessed in the intracranial self-stimulation (ICSS)
paradigm. A single intraperitoneal injection of LPS was used to induce a
pro-inflammatory immune response in male serotonin transporter wild type
(SERT(+/+)), heterozygous (SERT(+/-)) and knockout (SERT(-/-)) rats. Body weight
and ICSS thresholds were measured daily. Although LPS reduced body weight in all
genotypes, loss of body weight was less pronounced in SERT(-/-) compared to
SERT(+/+) rats. Remarkably, LPS-induced anhedonia was totally abolished in
SERT(-/-) rats and as expected was still present in SERT(+/+) and to a lesser
extent in SERT(+/-) rats. Therefore, it is concluded that an intact SERT function
is needed for pro-inflammatory cytokine-induced anhedonia and weight loss in
rats.
Copyright © 2013 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2012.12.013
PMID: 23274951 [Indexed for MEDLINE]