The purposes of this project were: 1) the determine alterations of the metabolism of enkephalin and dynorphin in the limbic- basal ganglia regions after electroconvulsive shock (ECS) or amygdaloid kindling; 2) to study the possible roles of brain opioid peptides in the development or maintenance of kindling-induced seizures. Repeated ECS produced an increase in the tissue level of both enkephalin and dynorphin in most of the limbic-basal ganglia regions, e.g. hypothalamus, amygdala and striatum. However, the most interesting alteration after ECS was in the hippocampus: an increase in enkephalin level but a drastic decrease in dynorphin level. Measurement of mRNA abundance by Northern blot indicated that repeated ECS increased the biosynthesis of enkephalin but decreased that of dynorphin. This differential regulation to these two opioid peptides may be related to the changes in opioid receptor mechanism in the hippocampus after repeated ECS. It is believed that enkephalin has a high affinity in binding to delta receptors whereas dynorphin-(1-8) mainly acts on mu receptors. Repeated ECS- induced up-regulation in mu receptors and down-regulation in delta receptors may be a consequence of a decrease in the activity of dynorphin-containing neurons and an increase in the activity of enkephalin-containing neurons. These differential modulations of opioid peptides and receptors after repeated ECS strongly suggest that opioid mechanisms play an important role in regulating the neuronal excitability of the hippocampus. In comparison to the effect of repeated ECS, amygdaloid kindling produced changes in the level of enkephalin and dynorphin in limited regions, such as amygdala, substantia nigra and hippocampus. The kindling-induced differential changes in enkephalin and dynorphin in the hippocampus was comparable to those of repeated ECS, suggesting that the hippocampal opioid systems are sensitive to seizures. Pretreatment with opiate receptor antagonists facilitate the rate of kindling suggesting a role of opioid peptides in the initiation of kindling.
