POWERFUL INHIBITION OF KAINIC ACID SEIZURES BY NEUROPEPTIDE-Y VIA Y5-LIKE RECEPTORS

Neuropeptide Y (NPY) is widely distributed in interneurons of the cent ral nervous system (CNS), including the hippocampus and cerebral corte x, in concentrations exceeding those of any other known neuropeptides( 1,2). Sequence data comparing different species show that NPY is highl y conserved(3). This suggests a critical role in regulation of regiona l neuronal excitability. Kainic acid, a glutamate agonist at kainic ac id receptors, causes severe limbic motor seizures culminating in statu s epilepticus(4). We here report that NPY administered into the latera l ventricle is a powerful inhibitor of motor as well as electroencepha lographic (EEC) seizures induced by kainic acid. This effect was media ted via receptors with a pharmacological profile similar to the recent ly cloned rat Y5 receptor(5). The present study is the first to demons trate that NPY possesses anticonvulsant activity. This is consistent w ith the concept that NPY is an endogenous anticonvulsant and suggests that agonists acting at Y5-like receptors may constitute a novel group of drugs in antiepileptic therapy.