Changes in extracellular glutamate and GABA levels in the hippocampal CA3 and CA1 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 CA1 and CA3 areas were separately assessed by brain microdialysis, and extracelluar glutamate and GABA were measured through the course of the seizures after a systemic administration 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 CA3 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 CA3 followed the diazepam injection. In the CA1 area, in contrast, a long-lasting decrease of extracellular glutamate was observed. The extracellular GABA concentration in the CA3 area increased immediately after the systemic administration of KA and returned to the normal 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 CA1 area, an increase of extracellular GABA began at about 3.5 h after KA administration (much later than that observed in the CA3 area) and was maintained throughout the observation. In situ hybridization showed 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 GAD65 mRNA was unaffected. GABA immunoreactivity in the same area and mossy fibers in the CA3 were increased most significantly at 8 h after administration of KA. The possible relation of GABA induction in mossy fibers with the delayed increase in extracellular GABA in CA3 was discussed.