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

Neuropeptide Y (NPY) and different NPY receptor (Y) subtype-selective agoni sts were tested for their effects on spontaneous epileptiform discharges wh ich developed in rat cortical and hippocampal slices in Mg2+-free medium. E pileptiform activity, recorded extracellularly, was attenuated by NPY(0.5-1 mu M) in both the frontal cortex and hippocampal CA3/CA1 pyramidal cell la yers. In the cortex the Y-1/5 selective agonist [Leu(31)Pro(34)] Npy was mo re effective than the Y, preferring agonist NPY13-36 and the Y-2/5 preferri ng agonist NPY3-36 The suppression of epileptiform discharges induced by NP Y 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, NPY13-36 and NPY3-36 were more effective than [Leu(3 1) Pro(34)] NPY. In conclusion, the antiepileptic activity of NPY is mediat ed 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. (C) 1999 El sevier Science Ireland Ltd. All rights reserved.