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
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1. Brain Behav Immun. 2013 Mar;29:98-103. doi: 10.1016/j.bbi.2012.12.013. Epub 2012
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
(1)Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences,
Utrecht University, Faculty of Science, Universiteitsweg 99, Utrecht, The
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
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PMID: 23274951 [Indexed for MEDLINE]