Systemic kainic acid administration in rats: Effects on kynurenic acid production in vitro and in vivo

Abstract

The endogenous broad spectrum excitatory amino acid receptor antagonist kynurenic acid (KYNA) has anti-convulsant properties and has been hypothetically linked to the pathogenesis of seizure disorders. Using brain slices and in vivo microdialysis in unanesthetized rats, KYNA synthesis from its bioprecursor kynurenine was therefore examined in the kainate model of temporal lobe epilepsy. Tissue slices obtained during status epilepticus from animals injected with kainate (10mg/kg, sc) did not show changes in KYNA production. One month after kainate injection, KYNA synthesis was substantially increased in slices of piriform cortex (380% of control) and hippocampus (227% of control) but not in striatal slices. Since KYNA production takes place preferentially in glia, these increases are likely to be due to the selective neuronal loss and reactive astrogliosis known to exist in chronically kainate-lesioned brains. Microdialysis, performed in the piriform cortex only, confirmed the in vitro results. Thus, no change in extracellular KYNA concentration was detected within 4 h after systemic kainate administration but a significant increase was observed 1 month later. Moreover, the veratridine-induced decrease in KYNA production detectable in normal tissue was not observed in the neuron-depleted piriform cortex. The data are discussed with regard to a possible role of gliaderived KYNA in temporal lobe epilepsy.