Repeated inhibitory effects of NPY on hippocampal CA3 seizures and wet dogshakes

Intracerebroventricular injection of NPY inhibits epileptiform seizures and seizure-related "wet dog shakes" (WDS) following electrical stimulation of the dentate gyrus or subiculum. This study examined the effects of NPY on seizures and WDS elicited in hippocampal CA3. Like in the other hippocampal regions, NPY significantly inhibited both seizures and accompanying WDS co nsistent with in vitro data. The identification of an additional antiepilep tic hippocampal target for NPY could prove therapeutically relevant conside ring that the hippocampal formation is a frequent seizure focus in human ep ilepsy. The effects of NPY were found to persist on seven repeated NPY inje ction days. Thus tolerance to the anti-seizure effects of NPY does not appe ar to develop rapidly. Tolerance being a problem with several current antie pileptic drugs, this further strengthens the concept of NPY receptors as a potential future antiepileptic target. (C) 2001 Elsevier Science Inc. All r ights reserved.