Taurine potentiates the anticonvulsive effect of the GABAA agonist muscimol and pentobarbital in the immature mouse hippocampus

Objective The high incidence of epileptic seizures in neonates and their frequent refractoriness to pharmacologic therapies require identification of new therapeutical options. Therefore, we investigated whether the modulatory effect of taurine on gamma-aminobutyric acid (GABA)(A) receptors can enhance the anticonvulsive potential of the GABA(A) receptor agonist muscimol and of the barbiturate pentobarbital. Methods We performed field potential recordings in in toto hippocampus preparations of immature (postnatal days 4-7) C57Bl/6 mouse pups. Spontaneous epileptiform activity was induced by the continuous presence of the potassium channel blocker 4-aminopyridine and the glycinergic antagonist strychnine in Mg2+-free solutions. Results Bath application of 0.1 mu mol/L muscimol increases the occurrence of recurrent epileptiform discharges, whereas they are significantly attenuated in a dose-dependent manner by muscimol in concentrations between 0.5 and 5 mu mol/L. Taurine at concentrations between 0.1 and 0.5 mmol/L induces a proconvulsive effect, but upon coapplication, it significantly augments the anticonvulsive effect of moderate muscimol doses (0.5-1 mu mol/L). In addition, the anticonvulsive effect of 100 and 200 mu mol/L pentobarbital is increased significantly in the presence of 0.5 mu mol/L taurine. <