title: Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter knockout rats: an intracranial self-stimulation study.
abstract: 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.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: F.vanHeesch@uu.nl.
authors.forename: Floor
authors.initials: F
authors.lastname: van Heesch
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Prins
authors.affiliation: Psychoneuroimmunology, Nutrition and Genetics, Victor Segalen Bordeaux 2 University, Bordeaux, France.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Koen G C
authors.initials: KGC
authors.lastname: Westphal
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: S Mechiel
authors.initials: SM
authors.lastname: Korte
mesh_terms: D000704:Analysis of Variance; D059445:Anhedonia / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D019540:Area Under Curve; D001427:Bacterial Toxins / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D012653:Self Stimulation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D050486:Serotonin Plasma Membrane Transport Proteins; C034151:heat stable toxin (E coli)