Region-specific changes in prodynorphin mRNA and ir-dynorphin A levels after kindled seizures

The opioid peptide dynorphin is thought to be implicated in specific types of seizures. In particular, complex partial seizures have been shown to cau se release of dynorphin, activation of prodynorphin gene expression, and ne w peptide synthesis in the hippocampus. In this study, the kinetics of the seizure-induced changes in prodynorphin mRNA and ir-dynorphin A levels in t he hippocampus have been compared with those induced in the temporal and fr ontal cortex, i.e., in other regions involved in the pathophysiology of com plex partial seizures. Experiments have been run using kindling, one of the most valuable models of partial epilepsy. In the hippocampus (1) prodynorp hin mRNA levels transiently increase (threefold) 1 h after kindled seizures , and return to baseline by 2 h, and (2) dynorphin A levels are slightly de creased at 1 h, but increase (twofold) at 2 h and return to baseline by 6 h . In the temporal and in the frontal cortex, a late (beginning at 2 h) and prolonged (up to 24 h) decrease in both prodynorphin mRNA and ir-dynorphin A levels have been observed. These data suggest that differential changes i n dynorphin metabolism occur in different brain areas after seizures. The m echanisms and functional implications of this observation remain to be inve stigated.