Autoradiographic analysis of neuropeptide Y receptor binding sites in the rat hippocampus after kainic acid-induced limbic seizures

Changes in peptide YY receptor binding were investigated at various intervals after limbic seizures induced in rats by an intraperitoneal injection of kainic acid (10-12 mg/kg). Six to 24 h after kainic acid, specific peptide YY binding, representing Y-1 and Y-2 neuropeptide Y receptor subtypes, was markedly enhanced in the strata radiatum and oriens CA3 (increase by up to 185% and 178% of control values, respectively). Seven and 30 days after kainic acid, a reduction by up to 63% was found. The basal and kainic acid-induced changes in peptide YY binding were mainly represented by Y-2 receptor sites. In the hilus of the dentate gyrus, an increase of global peptide YY binding by up to 400% was observed after 24 h which became attenuated to 125% after 30 days. In the molecular layer of the dentate gyrus global peptide YY binding increased by up to 87% between six and 24 h after kainic acid injection and was reduced by 37% after 30 days. Similar changes were observed in the cerebral cortex. Whereas in the hilus of the dentate gyrus peptide YY binding consisted mainly of Y-2 sites, it represented predominantly Y-1 receptors in the molecular layer and the cortex. The decline in global and Y-2 specific peptide YY binding observed at 30 days in the hippocampus proper was prevented in animals protected from seizure-induced brain damage by an anticonvulsant dose of phenobarbital 3 h after injection of kainic acid. In the stratum moleculare of the dentate gyrus, Y-2 specific binding was significantly enhanced while global peptide YY binding was slightly decreased compared to controls. These results show lasting changes in neuropeptide Y receptor binding sites after the acute seizures induced by kainic acid. Since neuropeptide Y modulates glutamatergic neurotransmission, these modifications may play an important role in the hippocampal excitability of chronically epileptic rats.