ELECTRICAL KINDLING IS ASSOCIATED WITH A LASTING INCREASE IN THE EXTRACELLULAR LEVELS OF KYNURENIC ACID IN THE RAT HIPPOCAMPUS

Endogenous kynurenic acid (KYNA), an excitatory amino acid receptor an tagonist with antineurotoxic and anticonvulsant: activity, was assesse d by microdialysis in the hippocampus of kindled rats. One week after the completion of amygdala or hippocampal kindling (stage 5), the dial ysate concentration of KYNA in the hippocampus of both hemispheres was 1.7 +/- 0.1-fold higher than in shams (P < 0.01). Veratridine (50 mu M), applied through the probe, reduced extracellular KYNA by 28% withi n 1 h in controls (P < 0.05), but was ineffective in stage 5 kindled r ats. At the preconvulsive stage 2, dialysate KYNA concentration and th e effect of veratridine were similar to controls. The activity of KYNA 's biosynthetic enzyme, kynurenine aminotransferase, did not change in the hippocampus I week after stage 5 seizures. These data indicate an enhanced liberation of KYNA in the hippocampus of fully kindled anima ls due to an impairment of normal regulatory mechanisms. This may be o f relevance for the control of hippocampal excitability during epilept ogenesis.