Document Detail


Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation.
MedLine Citation:
PMID:  22176740     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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)-1β and tumour necrosis factor (TNF)-α, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor κB] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor γ). 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.
Authors:
Karina S Macdowell; Borja García-Bueno; José L M Madrigal; Mara Parellada; Celso Arango; Juan A Micó; Juan C Leza
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-16
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  -     ISSN:  1469-5111     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-15     Citation Subset:  -    
Affiliation:
Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain.
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