Kinin B1receptors mediate depression-like behavior response in stressed mice treated with systemic E. coli lipopolysaccharide

Background: kinin b1receptors are inducible molecules up-regulated after inflammatory stimuli. this study evaluated the relevance of kinin b1receptors 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 b1receptor 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 b1receptor 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 b1receptor 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.conclusion: our data show,for the first time,involvement of kinin b1receptors in depressive behavioral responses,in a process likely associated with microglial activation and tnfα production. thus,selective and orally active b1receptor antagonists might well represent promising pharmacological tools for depression therapy. © 2010 viana et al; licensee biomed central ltd.