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 Y1 and Y2 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 Y2 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 Y2 sites, it represented predominantly Y1 receptors in the molecular layer and the cortex. The decline in global and Y2 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, Y2 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.
Röder
C
C
Department of Pharmacology, University Innsbruck, Austria.
Schwarzer
C
C
Vezzani
A
A
Gobbi
M
M
Mennini
T
T
Sperk
G
G
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000009:adverse effects*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced*
D017476:Receptors, Neuropeptide Y; D007608:Kainic Acid