PRETREATMENT WITH L-KYNURENINE, THE PRECURSOR TO THE EXCITATORY AMINO-ACID ANTAGONIST KYNURENIC ACID, SUPPRESSES EPILEPTIFORM ACTIVITY IN COMBINED ENTORHINAL HIPPOCAMPAL SLICES/

The kynurenine pathway converts tryptophan into various compounds, inc luding L-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid. The hypothesis that end ogenously-produced kynurenic acid could have physiological effects was tested in combined entorhinal/hippocampal slices from adult rats. Spe cifically, perfusion with L-kynurenine (1 mM) was examined for its abi lity to suppress epileptiform activity produced by subsequent perfusio n with buffer lacking added magnesium (nominal 0 mM magnesium buffer). Importantly, treatment with L-kynurenine did not appear to have depre ssant effects in itself, but it prevented spontaneous epileptiform act ivity in all 64 slices subsequently perfused with 0 mM magnesium buffe r. In contrast, 45 slices that were not pretreated with L-kynurenine e xhibited spontaneous epileptiform activity. These data support the hyp othesis that endogenously-produced kynurenic acid can be produced and released in brain slices, where it can suppress excitatory activity in an 'anticonvulsant' manner. Therefore, manipulation of the kynurenine pathway might constitute a useful new direction for anticonvulsant dr ug development. (C) 1997 Elsevier Science ireland Ltd.