The specific aims of this project are 1) to determine whether AP1 induction is due to the seizure behavior or to drug administration, 2) to examine any qualitative differences in AP1 transcription factor complexes in the rat hippocampus in acute chronic seizure paradigms, 3) to examine the pharmacological differences between acute metrazol and kainate treatments in the induction of AP1 transcription factors in the rat hippocampus, and 4) to elucidate whether opioid genes, which are transcriptionally modulated In these seizure paradigms, are directly regulated by AP1 transcription factors. Preliminary studies indicate that kainate induction of AP1 DNA binding in the rat hippocampus is delayed but is of long duration. A similar time course is observed with the expression of c-fos and the fos-related antigens. The anticonvulsant drugs, pentobarbital and diazepam, completely block the induction of AP1 DNA binding, while valproate caused only a 50% decrease in this effect. However, a dose response of kainate reveals a dose-dependent Increase in AP1 DNA binding that is independent of seizure activity since not all the rats are responsive to kainate. Rats repeatedly injected with kainate become tolerant to kainate, but AP1 DNA binding in the hippocampal protein is equivalent to animals that have undergone seizures. Subseizure doses of metrazol increase AP1 DNA binding. Therefore, these preliminary data suggest that the drug administration, not the seizure behavior, is responsible for the induction of AP1 DNA binding.
