SEIZURE RELATED CHANGES IN THE REGULATION OF OPIOID GENES AND TRANSCRIPTION FACTORS IN THE DENTATE GYRUS OF RAT HIPPOCAMPUS

An in situ hybridization study showed that limbic seizures induced by kainate strongly augmented the prodynorphin and proenkephalin messenge r RNA levels in granular cells of the rat hippocampal dentate gyrus. P entylenetetrazole increased the level of proenkephalin messenger RNA, but slightly decreased that of prodynorphin messenger RNA in the denta te gyrus. Administration of kainate to rats caused a profound increase in messenger RNAs of the transcription factor genes c-fos and c-jun i n the dentate gyrus, followed by an increase in the level of the trans criptional complex activator protein-1 in hippocampal neurons. Pentyle netetrazole also elevated the formation of activator protein-1, but th e effect appeared earlier than that induced by kainate. Thus, recurren t limbic seizures activate both prodynorphin and proenkephalin genes, whereas generalized clonic-tonic seizures seem to decrease the prodyno rphin and increase the proenkephalin gene expression in the dentate gy rus. Furthermore, our present results suggest that the transcription f actors, c-fos, c-jun and activator protein-1 complex may be involved i n the process of inducing the hippocampal proenkephalin gene, while th ese factors might be differently involved in regulation of prodynorphi n gene expression.