Differential effects of allopregnanolone and GABA on kainate-induced lactate dehydrogenase release in cultured rat cerebral cortical cells

To exam the effects of allopregnanolone and gamma-amino-butyric acid (GABA) on the excitotoxicity. The excitotoxicity was evoked by kainate (KA) in the primary culture of rat cerebral cortical cells. Effect of allopregnanolone or GABA on the excitotoxicity was examined by the measurement of lactate dehydrogenase (LDH) activity released in the culture medium. Either acute (3 h) or chronic (24 h) treatment with KA (0.01-1 mmol/L) produced a concentration-dependent increase in LDH activity released. The EC50 values were (0.16+/-0.03) mmol/L and (0.257+/-0.015) mmol/L, respectively. Acute treatment with allopregnanolone (10-1000 nmol/L) for 3 h did not significantly affect the 0.2 mmol/L KA-induced LDH activity. On the other hand, chronic treatment with allopregnanolone (10-1000 nmol/L) for 24 h, produced inhibition on the KA-induced LDH activity in a concentration-dependent manner. The EC50 value was (436+/-19) nmol/L. Acute treatment with GABA (0.1-100 micromol/L) exacerbate the 0.2 mmol/L KA-induced LDH activity in a concentration-dependent manner, with an EC50 value of (2.7+/-1.0) micromol/L; while chronic treatment with GABA had no significant effect. There were differential patterns between the effects of allopregnanolone and GABA on the KA-induced excitotoxicity.