Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 16, Issue 1, Pages 121-135Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145711001775
Keywords
Antipsychotics; LPS; neuroinflammation; risperidone; schizophrenia
Funding
- Instituto de Salud Carlos III, MCINN [FIS 10/123]
- Instituto de Salud Carlos III, MCINN (Centro de Investigacion en Red de Salud Mental, CIBERSAM)
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Inflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra-and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra-and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. Main results : single doses of risperidone (0.3-3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor kappa B] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor c). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells.
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