CHANGES IN EXTRACELLULAR GLUTAMATE AND GABA LEVELS IN THE HIPPOCAMPALCA(3) AND CA(1) AREAS AND THE INDUCTION OF GLUTAMIC-ACID DECARBOXYLASE-67 IN DENTATE GRANULE CELLS OF RATS TREATED WITH KAINIC ACID

For the evaluation of glutamatergic and GABAergic transmission during seizures, rat hippocampal CA(1) and CA(3) areas were separately assess ed by brain microdialysis, and extracelluar glutamate and GABA were me asured through the course of the seizures after a systemic administrat ion of kainic acid (KA). The generalized convulsion started at about 1 .5 h and was suppressed by diazepam at 2 h after the KA treatment. In the CA(3) area, extracellular glutamate started to increase soon after the KA injection and returned to the control level at about 1.5 h. A decrease and then slight increase of the extracellular glutamate level in CA(3) followed the diazepam injection. In the CA(1) area, in contr ast, a long-lasting decrease of extracellular glutamate was observed. The extracellular GABA concentration in the CA(3) area increased immed iately after the systemic administration of KA and returned to the nor mal level at about 3.5 h. A second increase in the extracellular GABA in this area began at about 4.5 h after the KA treatment. In the CA(1) area, an increase of extracellular GABA began at about 3.5 h after KA administration (much later than that observed in the CA(3) area) and was maintained throughout the observation. In situ hybridization showe d a transient expression of glutamic acid decarboxylase (GAD)-67 mRNA in the granule cell layer of the dentate gyrus at 4 and 6 h, whereas G AD65 mRNA was unaffected. GABA immunoreactivity in the same area and m ossy fibers in the CA(3) were increased most significantly at 8 h afte r administration of KA. The possible relation of GABA induction in mos sy fibers with the delayed increase in extracellular GABA in CA(3) was discussed. (C) 1998 Elsevier Science B.V. All rights reserved.