STATUS OF SOMATOSTATIN RECEPTOR MESSENGER-RNAS AND BINDING-SITES IN RAT-BRAIN DURING KINDLING EPILEPTOGENESIS

In situ hybridization histochemistry with somatostatin sst(1)-sst(5) r eceptor messenger RNA-selective oligoprobes and quantitative receptor autoradiographic binding studies using [I-125]Tyr(3)-octreotide, [Leu( 8), D-Trp(22),I-125-Tyr(25)]somatostatin-28 and [I-125]CGP 23996 25]c[ Asn-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) were performed to determ ine the level of expression of somatostatin receptor messenger RNA and receptor binding sites in the hippocampal formation, limbic system an d cerebral cortex of adult rats electrically kindled in the dorsal hip pocampus. In control rats (implanted with electrodes but not electrica lly stimulated), the somatostatin-1 receptor-selective [I-125]Tyr(3)-o ctreotide and the non-subtype-selective [LeU(8),D-Trp(22),I-125-Tyr(25 )]somatostatin-28 preferentially labelled the strata oriens and radiat um of the CA1 subfield of the hippocampus, the molecular layer of the dentate gyrus, the subiculum and presubiculum of the hippocampal forma tion, the inner layer of the frontal cortex, and the lateral and basol ateral nuclei of the amygdala. The non-subtype-selective radioligand [ I-125]CGP 23996 (in 5 mM Mg2+ buffer) preferentially labelled the stra ta oriens and radiatum of the CA1 subfield of the hippocampus, the sub iculum and the basolateral nucleus of the amygdala. Under conditions w here primarily somatostatin-2 receptors were labelled, [I-125]CGP 2399 6 (in 120 mM Na+ buffer) showed strong binding in the strata oriens an d radiatum of the CA1 subfield of the hippocampus and the frontal cort ex, whereas the dentate gyrus, subiculum and amygdala showed only weak signals. During and after kindling, no significant differences were o bserved between the ipsi- and contralateral sides of the hippocampus. A significant decrease (about 40%) of somatostatin receptor binding si tes was observed in the molecular layer of the dentate gyrus with all radioligands (except [I-125]CGP 23996 in Na+ buffer, which did not lab el this area) at stage 2 (pre-convulsive stage) and one week, but not one month, after stage 5 (generalized motor seizures). In contrast to somatostatin receptor binding, no alterations of the messenger RNA lev els for sst(1)-sst(5) receptors were found either at stage 2 or at sta ge 5. Similarly, no changes in receptor binding or messenger RNA level s were observed in the brain of rats which experienced a single afterd ischarge. The present study shows a significant and selective decrease of somatostatin-1 receptor binding sites in the dentate gyrus of kind led rats. This is part of the plastic changes induced by kindling and may contribute to the increased sensitivity for the induction of gener alized seizures during kindling. Copyright (C) 1996 IBRO.