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

Abstract

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 γ-aminobutyric acid (GABA)A receptors can enhance the anticonvulsive potential of the GABAA receptor agonist muscimol and of the barbiturate pentobarbital. 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. Bath application of 0.1μmol/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 5μmol/L. Taurine at concentrations between 0.1 and 0.5mmol/L induces a proconvulsive effect, but upon coapplication, it significantly augments the anticonvulsive effect of moderate muscimol doses (0.5-1μmol/L). In addition, the anticonvulsive effect of 100 and 200μmol/L pentobarbital is increased significantly in the presence of 0.5μmol/L taurine. These observations demonstrate that taurine can indeed enhance the anticonvulsive effects of muscimol and pentobarbital, suggesting that taurine may act as a positive modulator on GABAA receptors. Thus, interfering with the modulatory taurine binding site of GABAA receptors or the interstitial taurine concentration may provide new therapeutical options for anticonvulsive therapies in neonates.