Differential effects of typical and atypical antipsychotics on astroglial cells in vitro

Astrocytes are glial cells that are essential for the maintenance of central nervous system functions, modulating neurotransmitters, providing metabolic, trophic and antioxidant support, and producing a wide range of cytokines to modulate the inflammatory response. These cells can be targets for antipsychotics, medications used in the treatment of neuropsychiatric disorders. In this regard, several studies have shown that antipsychotics are able to modulate peripheral cytokine release, but their effects on astroglial inflammatory response need to be further investigated. In this study, we evaluated the effects of risperidone and haloperidol, common atypical and typical antipsychotics, respectively, on cytokine release and redox status in C6 astroglial cells, an astrocyte-like cell line. Risperidone showed an anti-inflammatory activity, decreasing the release of tumor necrosis factor α (TNF-α), interleukins 1β (IL-1 β) and 6 (IL-6), and increasing interleukin 10 (IL-10). This atypical antipsychotic was also able to decrease the transcriptional activity of nuclear factor κB (NFκB) and improve glutathione content. However, haloperidol induced a pro-inflammatory response, increasing the extracellular levels of TNF-α and IL-1β, in addition to decreasing IL-10. This typical antipsychotic could induce an inflammatory response by activating p38 mitogen-activated protein kinase (p38 MAPK)/NFκB pathways. In summary, our results suggest that risperidone and haloperidol present different effects on astroglial cells, in this way being able to differentially affect the neuroinflammation associated with neuropsychiatric disorders.