Intracerebral administration of L-kynurenine decreases N-methyl-D-aspartate receptor-mediated production of cGMP in the cerebellum and hippocampus ofunanaesthetized rats subjected to transcerebral microdialysis

The effects of intracerebral administration of L-kynurenine (L-KYN) on the N-methyl-D-aspartate (NMDA) receptor-mediated, nitric oxide (NO)-dependent cGMP responses have been studied in vivo in the cerebellum and hippocampus of freely-moving rats subjected to transcerebral microdialysis. Administrat ion of exogenous NMDA in the cerebellum through the dialysis probe evoked a 3-fold increase of basal extracellular levels of cGMP that was concentrati on-dependently reduced by co-infusion of L-KYN. In the hippocampus, local a dministration of cyclothiazide caused a significant enhancement of the cycl ic nucleotide dialysate concentrations that was accompanied by behavioural manifestations characteristic of preconvulsive states. Go-infusion of L-KYN largely decreased the neurochemical effects of cyclothiazide and completel y prevented the appearance of the behavioural episodes. It is concluded tha t administration of L-KYN by increasing endogenous kynurenic acid concentra tions might exert neuroprotective and anticonvulsive effects through blocka de of the NMDA receptor/NO/cGMP pathway. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.