Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter knockout rats: an intracranial self-stimulation study

Brain Behav Immun. 2013 Mar:29:98-103. doi: 10.1016/j.bbi.2012.12.013. Epub 2012 Dec 28.


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.

MeSH terms

  • Analysis of Variance
  • Anhedonia / drug effects*
  • Anhedonia / physiology
  • Animals
  • Animals, Genetically Modified
  • Area Under Curve
  • Bacterial Toxins / pharmacology
  • Body Weight / drug effects
  • Brain / physiology
  • Cytokines / pharmacology
  • Enterotoxins / pharmacology
  • Escherichia coli Proteins
  • Gene Deletion
  • Lipopolysaccharides / pharmacology*
  • Male
  • Rats
  • Self Stimulation
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / physiology*


  • Bacterial Toxins
  • Cytokines
  • Enterotoxins
  • Escherichia coli Proteins
  • Lipopolysaccharides
  • Serotonin Plasma Membrane Transport Proteins
  • heat stable toxin (E coli)