Considerable work in this laboratory has focused on the role of enkephalin and dynorphin in seizure activity and related sezuelae. Among other things, 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 Dy kainic acid or by stimulation of the perforant path (PP). The first objective of this project was to develop a method of electrical stimulation of the PP which would elicit WDS consistently and repeatedly in the absence of an overt seizure. Using this method, we have demonstrated that stimulation of PP under conditions which elicit WDS produces a significant decrease in hippocampal levels of enkephalin and dynorphin. Levels of these substances are not altered by stimulus parameters insufficient to elicit WDS. Moreover, intraventricular injection of either an opioid mu receptor (beta-FNA) or delta receptor (ICI174864) antagonist reduced the number of WD5 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. Current studies have demonstrated that naloxone, an opioid antagonist, reduces the number of WDS and tends to shorten the duration of electrical seizure activity induced by PP stimulation. The most striking effect of naloxone, however, is to markedly reduce the number of WDS at short (<.50 sec) durations of seizure activity. Lesion studies have demonstrated that a site involving the DGCs within the ventral hippocampus is critical for elicitation of WD5 by PP stimulation. Studies in progress concern the nature of the differences between the dorsal and ventral hippocampus responsible for this phenomenon.
