title: Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation.
abstract: 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.
  
  
  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.affiliation: Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Karina S
authors.initials: KS
authors.lastname: MacDowell
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.forename: José L M
authors.initials: JL
authors.lastname: Madrigal
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.forename: Juan A
authors.initials: JA
authors.lastname: Micó
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018967:Risperidone