Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation

The extracellular l-glutamate (l-glu) concentration is elevated in neuroinflammation,thereby causing excitotoxicity. one of the mechanisms is down-regulation of astrocyte l-glu transporters. some antidepressants have anti-inflammatory effects. we therefore investigated effects of various antidepressants on the down-regulation of astrocyte l-glu transporters in the in vitro neuroinflammation model. among these antidepressants,only paroxetine was effective. we previously demonstrated that the down-regulation of astrocyte l-glu transporters was caused by l-glu released from activated microglia. we here clarified that only paroxetine inhibited l-glu release from microglia. this is the novel action of paroxetine,which may bring advantages on the therapy of neuroinflammation. © 2014 japanese pharmacological society.