Electrical kindling is associated with a lasting increase in the extracellular levels of kynurenic acid in the rat hippocampus

Endogenous kynurenic acid (KYNA), an excitory amino acid receptor antagonist with antineurotoxic and anticonvulsant activity, was assessed by microdialysis in the hippocampus of kindled rats. One week after the completion of amygdala or hippocampal kindling (stage 5), the dialysate concentration of KYNA in the hippocampus of both hemispheres was 1.7 ± 0.1-fold higher than in shams (P <0.01). Veratridine (50 μM), applied through the probe, reduced extracellular KYNA by 28% within 1 h in controls (P <0.05), but was ineffective in stage 5 kindled rats. At the preconvulsive stage 2, dialysate KYNA concentration and the effect of veratridine were similar to controls. The activity of KYNA's biosynthetic enzyme, kynurenine aminotransferase, did not change in the hippocampus 1 week after stage 5 seizures. These data indicate an enhanced liberation of KYNA in the hippocampus of fully kindled animals due to an impairment of normal regulatory mechanisms. This may be of relevance for the control of hippocampal excitability during epileptogenesis.