Our work focused on the role of enkephalin and dynorphin in seizure activity and related sequalae. This work implicated enkephalin as playing a major role in the elucidation of a phenomenon in rats known as """"""""wet dog shakes"""""""" (WDS). This study has also implicated the dentate granule cells (DCGs) as being necessary for the elicitation of WDS at least with respect to induction by kainic acid or by stimulation of the perforant path (PP). We demonstrated that stimulation of PP under conditions which elicit WDS produces a significant decrease in hippocampal levels of enkephalin and dynorphin. Moreover, intraventricular injection of either an opioid mu receptor (beta-FNA) or delta receptor (ICII174864) antagonist reduced the number of WDS elicited by PP stimulation. These data provide the first evidence that endogenous opioids are released by PP stimulation and lend further support to the notion that they play a role in regulation of hippocampal excitability. We also demonstrated that the opioid receptor antagonist, naltrexone, when injected directly into the ventral hippocampus, produces an elevation in the threshold for eliciting wet dog shakes. We demonstrated that destruction of dentate granule cells in the ventral, but not dorsal, hippocampal formation abolishes WDS induced by PP or intrahippocampal stimulation or by systemic administration of kainic acid. It was also found that slices obtained from the ventral portion of the hippocampus have a lower threshold for epileptiform bursting induced by an opioid mu receptor than slices from the dorsal end. Thus, these studies clearly demonstrate differences between the ventral and dorsal portions of the hippocampus. Recent studies examined (1) changes in opioid receptors induced by stimulation of the perforant path and (2) changes in enkephalin and dynorphin levels in the hippocampus as a result of destruction of the DGCs. This project was terminated in January. 1993 due to retirement of PI.
