Neuropeptide Y suppresses epileptiform activity in rat frontal cortex and hippocampus in vitro via different NPY receptor subtypes

Abstract

Neuropeptide Y (NPY) and different NPY receptor (Y) subtype-selective agonists were tested for their effects on spontaneous epileptiform discharges which developed in rat cortical and hippocampal slices in Mg 2+-free medium. Epileptiform activity, recorded extracellularly, was attenuated by NPY (0.5–1 μM) in both the frontal cortex and hippocampal CA3/CA1 pyramidal cell layers. In the cortex the Y 1/5 selective agonist [Leu 31Pro 34] NPY was more effective than the Y 2 preferring agonist NPY 13–36 and the Y 2/5 preferring agonist NPY 3–36. The suppression of epileptiform discharges induced by NPY in cortical slices was blocked by the selective Y 1 receptor antagonist ( R)- N 2-(diphenylacetyl)- N-[(4-hydroxyphenyl)methyl] argininamide (BIBP 3226). In the hippocampus, NPY 13–36 and NPY 3–36 were more effective than [Leu 31 Pro 34] NPY. In conclusion, the antiepileptic activity of NPY is mediated predominantly by the Y 1 receptor subtype in the frontal cortex and by Y 2 and probably Y 5 receptors in the hippocampal CA3/CA1 areas.