Seizure related changes in the regulation of opioid genes and transcription factors in the dentate gyrus of rat hippocampus

Neuroscience. 1995 Sep;68(1):73-81. doi: 10.1016/0306-4522(95)00144-8.


An in situ hybridization study showed that limbic seizures induced by kainate strongly augmented the prodynorphin and proenkephalin messenger RNA levels in granular cells of the rat hippocampal dentate gyrus. Pentylenetetrazole increased the level of proenkephalin messenger RNA, but slightly decreased that of prodynorphin messenger RNA in the dentate gyrus. Administration of kainate to rats caused a profound increase in messenger RNAs of the transcription factor genes c-fos and c-jun in the dentate gyrus, followed by an increase in the level of the transcriptional complex activator protein-1 in hippocampal neurons. Pentylenetetrazole also elevated the formation of activator protein-1, but the effect appeared earlier than that induced by kainate. Thus, recurrent limbic seizures activate both prodynorphin and proenkephalin genes, whereas generalized clonic-tonic seizures seem to decrease the prodynorphin and increase the proenkephalin gene expression in the dentate gyrus. Furthermore, our present results suggest that the transcription factors, c-fos, c-jun and activator protein-1 complex may be involved in the process of inducing the hippocampal proenkephalin gene, while these factors might be differently involved in regulation of prodynorphin gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • DNA / metabolism
  • Dentate Gyrus / metabolism*
  • Enkephalins / biosynthesis
  • Enkephalins / genetics
  • Gene Expression Regulation / physiology*
  • Genes, fos
  • Genes, jun
  • Kainic Acid
  • Male
  • Opioid Peptides / biosynthesis*
  • Opioid Peptides / genetics
  • Pentylenetetrazole
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / metabolism*
  • Transcription Factor AP-1 / biosynthesis
  • Transcription Factors / metabolism*


  • Enkephalins
  • Opioid Peptides
  • Protein Precursors
  • RNA, Messenger
  • Transcription Factor AP-1
  • Transcription Factors
  • proenkephalin
  • DNA
  • preproenkephalin
  • Kainic Acid
  • Pentylenetetrazole