The purposes of this project were: 1) to determine alterations of the metabolism of enkephalin and dynorphin in the limbic-basal ganglia regions after electrical stimulation-induced (electroconvulsive shock (ECS), or amygdaloid kindling) or chemical-induced (kainic acid (KA)) seizures; 2) to study the possible roles of brain opioid peptides in the expression of preseizure behaviors, such as wet dog shakes (WDS) or seizure activities after KA administration. Both repeated ECS and amygdaloid kindling produced a profound alteration of the metabolism of both enkephalin and dynorphin in different brain regions. Repeated ECS caused an increase in the level of (Met5)-enkephalin-like immunoreactivity (ME-LI) in the limbic-basal ganglia regions. Measurement of the abundance of mRNA coding for enkephalin suggested that the increase in ME-LI after repeated ECS is the result of an increased biosynthesis of this peptide. KA produces WDS and behavioral convulsions in the experimental animals. We have attempted to illucidate the possible relationship between hippocampal opioid peptides and KA-induced seizure-related behaviors. KA caused an initial release of both ME-LI and DN-LI during the period of recurrent convulsions which was followed by a large rebound in ME-LI and a modest increase in DN-LI 2 days later. We have obtained the following evidence suggesting that the profound change in the metabolism of enkephalin may be related to Ka-induced WDS. (1) Naloxone, an opiate antagonist, caused a dose-dependent attenuation of KA-induced WDS. (2) Intraventricular injection of antibodies against (Met5)-enkephalin, but not dynorphin A (1-8) caused a significant reduction in KA-induced WDS. (3) Colchicine lesions of ME and DYN containing granule cells eliminate KA-induced WDS. These results support the concept that enkephalin may mediate KA-induced WDS. We plan to employ more specific opiate agonists and antagonists injected to different brain regions in KA-treated rats in an attempt to further understand the roles of opioid peptides in seizures.
