TY - JOUR
T1 - Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter knockout rats
T2 - An intracranial self-stimulation study
AU - Van Heesch, F.
AU - Prins, J.
AU - Konsman, J.P.
AU - Westphal, K.G.C.
AU - Olivier, B.
AU - Kraneveld, A.D.
AU - Korte, S.M.
PY - 2013/3
Y1 - 2013/3
N2 - 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. © 2013 Elsevier Inc.
AB - 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. © 2013 Elsevier Inc.
UR - http://www.scopus.com/inward/record.url?scp=84873432955&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2012.12.013
DO - 10.1016/j.bbi.2012.12.013
M3 - Article
SN - 0889-1591
VL - 29
SP - 98
EP - 103
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -
