Work in this laboratory has focused on the role of enkephalin and dynorphin in seizure activity and related sequelae. This work has implicated enkephalin as playing a major role in the elucidation of a phenomenon in rats known as "wet dog shakes" (WDS). This work has also implicated the dentate granule cells (DGCs) 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 have 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 (ICII74864) 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 have 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 have also demonstrated that destruction of dentate granule cells in the ventral, but not dorsal, hippocampal formation abolishes wet dog shaking induced by perforant path or intrahippocampal stimulation or by systemic administration of kainic acid. It has also been 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. This is of importance since most previous studies have viewed the hippocampus as being functionally homogeneous. We have also found that destruction of DGCs (which deplete the hippocampus of dynorphin) results in a marked lowering of the threshold for induction of seizure activity elicited by PP stimulation.