UP-REGULATION OF NEUROPEPTIDE Y-Y-2 RECEPTORS IN AN ANIMAL-MODEL OF TEMPORAL-LOBE EPILEPSY

Receptor autoradiography with the Y-2, receptor ligand I-125-peptide Y Y3-36,,, and in situ hybridization were applied to investigate changes in neuropeptide tyrosine-Y-2, receptor expression after kainic acid-i nduced recurrent seizures in the rat hippocampus. In the strata oriens and radiatum of CAI to CA3, which are densely innervated by Y-2, rece ptor-bearing Schaffer collateral terminals, a transient 2-fold increas e in Y-2, receptor affinity was observed after 4-12 hr, with a later s low decline. No change was seen in Y-2, mRNA expression in CA2/CA3 pyr amidal cells, from which Schaffer collaterals originate. Conversely, i n granule cells of the dentate gyrus, markedly elevated Y-2, mRNA conc entrations were observed (by 740% in the dorsal hippocampus) 24-48 hr after kainate injection. At the same time, a marked and lasting (up to 6 months) increase in the number of Y-2, receptor sites (by 800%) was seen in the dentate hilus, which is innervated densely by mossy fiber s. The early increase in Y-2, receptor affinity in Schaffer collateral s was accompanied by a 60% decrease in the EC50,, of peptide YY3-36,, in inhibiting K+-stimulated glutamate release in hippocampal slices fr om kainic acid-treated rats. Our data indicate transient up-regulation of presynaptic Y-2, receptors in Schaffer collaterals by a change in affinity and a permanent de novo synthesis of presynaptic Y-2, recepto rs in granule cells/mossy fibers. These changes may cause augmented pr esynaptic inhibition of glutamate release from different hippocampal s ites and, in conjunction with increased concentrations of neuropeptide tyrosine in mossy fibers, may represent an endogenous reactive antico nvulsant mechanism.