Excitatory effects of kynurenine and its metabolites, amino acids and convulsants administered into brain ventricles: differences between rats and mice

Abstract

When introduced intracerebroventricularly, quinolinic acid appeared to be the only kynurenine metabolite among those tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitement and clonic seizures in rats; in high dosage all exhibited convulsant action in mice. L-Kynurenine sulfate (500 micrograms) induced continuous rotation in rats around a longitudinal axis in one or other direction. It also potentiated the convulsant effect of strychnine sulfate and caffeine. Neither the excitatory amino acids, L-glutamic and L-aspartic acids nor the inhibitory amino acids, GABA, glycine and taurine induced excitement or seizures in rats but did in mice. In rats, GABA, glycine and taurine induced sedation, side position and discoordination. The convulsants, strychnine sulfate and pentylenetetrazole, induced seizures both in rats and mice. Differences between species may derive from the better access of intracerebroventricularly administered drugs to mouse hippocampus. Thus mice may be preferable for studies of this type on excitatory amino acids (including kynurenine pathway metabolites) and rats for those on inhibitory amino acids.