Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainicacid

We have recently reported that dextromethorphan attenuates the neurotoxicit y induced by kainic acid in a dose-related fashion. Pretreatments with dext romethorphan (50 mg/kg, p.o. x2) significantly reduced the activator protei n-1 DNA-binding activity and the Fos-related antigen-immunoreactive protein induced by kainic acid (10 mg/kg, i.p.) in the CA1, but not the CA3 or the dentate gyrus sector of the rat hippocampus. Paradoxically, dextromethorph an itself caused an elevated activator protein-1 DNA-binding activity and F os-related antigen-immunoreactive protein in the CA1 region which lasted fo r at least 4 days. The results suggest that the CA1 area is the critical si te for mediating the putative neuroprotective effect induced by dextrometho rphan. (C) 1999 Elsevier Science B.V. All rights reserved.