EFFECTS OF PILOCARPINE AND KAINATE-INDUCED SEIZURES ON N-METHYL-D-ASPARTATE RECEPTOR GENE-EXPRESSION IN THE RAT HIPPOCAMPUS

The effects of pilocarpine- and kainate-induced seizures on N-methyl-D -aspartate receptor subunit-1 messenger RNA and [H-3]dizocilpine malea te binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-D-aspartate recep tor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h afte r drug injection. Both convulsants decreased the messenger RNA level i n CA1 pyramidal cells at 24 and 72 h, the effects of kainate being mor e profound. Kainate also decreased the N-methyl-D-aspartate receptor s ubunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h aft er kainate, but not pilocarpine, an increased binding of [H-3]dizocilp ine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [H-3]dizocilpine maleate binding in str atum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-D-aspartate rec eptor subunit-1 gene expression in dentate gyrus. However, at the late st lime measured, kainate had the stronger effect in decreasing both m essenger RNA N-methyl-D-aspartate receptor subunit-1 and [H-3]dizocilp ine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The la tter changes corresponded, however, to neuronal loss and may reflect h igher neurotoxic potency of kainate. These data point to some differen ces in hippocampal N-methyl-D-aspartate receptor regulation in pilocar pine and kainate models of limbic seizures. Moreover, our results sugg est that the N-methyl-D-aspartate receptor subunit-1 messenger RNA lev el is more susceptible to limbic seizures than is [H-3]dizocilpine mal eate binding in the rat hippocampal formation. (C) 1997 IBRO. Publishe d by Elsevier Science Ltd.