title: Kinin B1 receptors mediate depression-like behavior response in stressed mice treated with systemic E. coli lipopolysaccharide.
abstract: BACKGROUND
  Kinin B1 receptors are inducible molecules up-regulated after inflammatory stimuli. This study evaluated the relevance of kinin B1 receptors in a mouse depression behavior model.
  
  
  METHODS
  Mice were exposed to a 5-min swimming session, and 30 min later they were injected with E. coli lipopolysaccharide (LPS). Depression-like behavior was assessed by determining immobility time in a tail suspension test. Different brain structures were collected for molecular and immunohistochemical studies. Anhedonia was assessed by means of a sucrose intake test.
  
  
  RESULTS
  Our protocol elicited an increase in depression-like behavior in CF1 mice, as assessed by the tail-suspension test, at 24 h. This behavior was significantly reduced by treatment with the selective B1 receptor antagonists R-715 and SSR240612. Administration of SSR240612 also prevented an increase in number of activated microglial cells in mouse hippocampus, but did not affect a reduction in expression of mRNA for brain-derived neurotrophic factor. The increased immobility time following LPS treatment was preceded by an enhancement of hippocampal and cortical B1 receptor mRNA expression (which were maximal at 1 h), and a marked production of TNFα in serum, brain and cerebrospinal fluid (between 1 and 6 h). The depression-like behavior was virtually abolished in TNFα p55 receptor-knockout mice, and increased B1 receptor mRNA expression was completely absent in this mouse strain. Furthermore, treatment with SSR240612 was also effective in preventing anhedonia in LPS-treated mice, as assessed using a sucrose preference test.
  
  
  CONCLUSIONS
  Our data show, for the first time, involvement of kinin B1 receptors in depressive behavioral responses, in a process likely associated with microglial activation and TNFα production. Thus, selective and orally active B1 receptor antagonists might well represent promising pharmacological tools for depression therapy.
authors.affiliation: Pharmacology Department, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Viana
authors.forename: Izaque S
authors.initials: IS
authors.lastname: Maciel
authors.forename: Fabiana N
authors.initials: FN
authors.lastname: Dornelles
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Figueiredo
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Siqueira
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D006801:Humans; D007705:Kinins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007705:Kinins; D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1