Effect of allopregnanolone on d-[3H]-aspartate release and [3H]-glutamate uptake in the hippocampus of kainate-treated mice.

In order to determine whether the status epilepticus leads to alterations in the neurosteroid effect on excitatory amino acid transmission, we studied the influence of allopregnanolone on aspartate release and glutamate uptake in mouse hippocampus at various times after kainate administration. No significant differences in the K+-stimulated D-[3H]-aspartate release from the hippocampi of saline- and kainate-treated mice were observed; however, that parameter tended to fall in tissues collected I h after kainate administration. Allopregnanolone significantly attenuated the K+-stimulated D-[3H]-aspartate release from the hippocampi of control animals, as well at 24 h and 7 days after kainate injection; in contrast it did not affect amino acid release from the hippocampi collected 1 h after kainate administration. Kainate administration had no effect on [3H]-glutamate uptake after 1 and 24 h, but elevated that parameter on day 7. Allopregnanolone (10 and 100 microM) did not affect [3H]-glutamate uptake in control and kainate-treated mice. In conclusion, the present study indicates a loss of the inhibitory effect of allopregnanolone on the potasium-stimulated D-[3H]-aspartate release from mouse hippocampus during the kainate-induced status epilepticus; moreover, it excludes involvement of this neurosteroid in the regulation of hippocampal [3H]-glutamate uptake in both control and kainate-treated mice.