PHENIDONE BLOCKS THE INCREASES OF PROENKEPHALIN AND PRODYNORPHIN GENE-EXPRESSION INDUCED BY KAINIC ACID IN RAT HIPPOCAMPUS - INVOLVEMENT OFFOS-RELATED ANTIGENE PROTEIN

To determine the possible role of cyclooxygenase/lipoxygenase pathway in the regulation of proenkephalin (proENK) and prodynorphin (proDYN) gene expression induced by kainic acid (KA) in rat hippocampus, the ef fects of esculetin, aspirin, or phenidone on the seizure activity, pro ENK and proDYN mRNA levels, and the level of fos-related antigene (Fra ) protein induced by KA in rat hippocampus were studied. Esculetin (5 mg/kg), aspirin (15 mg/kg), or phenidone (50 mg/kg) was administered o rally five times every 12 h before the injection of KA (10 mg/kg, i.p. ). Seizure activity induced by KA was significantly attenuated by phen idone. However, neither esculetin nor aspirin affected KA-induced seiz ure activity. The proENK and proDYN mRNA levels were markedly increase d 4 and 24 h after KA administration. The elevations of both proENK an d proDYN mRNA levels induced by KA were inhibited by pre-administratio n with phenidone, but not with esculetin and aspirin. ProENK-like prot ein level increased by KA administration was also inhibited by pre-adm inistration with phenidone, but not with esculetin and aspirin. The in creases of proENK and proDYN mRNA levels induced by KA were well corre lated with the increases of Fra protein level. Additionally, the induc tion of Fra protein was inhibited by pre-administration with phenidone , but not with esculetin and aspirin. The results suggest that blockad e of both cyclooxygenase and lipoxygenase pathways appears to be respo nsible for increases of proENK and proDYN mRNA levels induced by KA vi a inhibiting the induction of Fra protein in rat hippocampus. (C) 1998 Elsevier Science B.V.