Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation.
Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain.
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 NFκB] 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.