title: Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.
abstract: BACKGROUND
  Activation of the tryptophan degrading enzyme indoleamine-2,3-dioxygenase 1 (IDO1) is associated with the development of behavioral signs of depression. Systemic immune challenge induces IDO1 in both the periphery and the brain, leading to increased circulating and brain concentrations of kynurenines. However, whether IDO1 activity within the brain is necessary for the manifestation of depression-like behavior of mice following a central immune challenge remains to be elucidated.
  
  
  METHODS
  We investigated the role of brain IDO1 in mediating depression-like behavior of mice in response to intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng).
  
  
  RESULTS
  LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution. These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine. Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test.
  
  
  CONCLUSIONS
  These data indicate that activation of brain IDO1 is sufficient to induce depression-like behaviors of mice in response to central LPS.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Lawson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Parrott
authors.forename: Robert H
authors.initials: RH
authors.lastname: McCusker
authors.forename: Robert
authors.initials: R
authors.lastname: Dantzer
authors.forename: Keith W
authors.initials: KW
authors.lastname: Kelley
authors.forename: Jason C
authors.initials: JC
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000172:deficiency* / Q000235:genetics; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D013395:Sucrose; D014364:Tryptophan; C525396:1-methyltryptophan