Changes in the gene expression of GABAA receptor subunit mRNAs in the septum of rats subjected to pentylenetetrazol-induced kindling.

Chemical kindling was induced in rats by long-term administration of pentylenetetrazol (PTZ) (30 mg/kg three times a week for 9 weeks). The effects of such kindling on the abundance of transcripts encoding subunits of the gamma-aminobutyric acid type A (GABAA) receptor in the brain were measured by RNase protection assay. Kindled rats were examined either 3 or 30 days after discontinuation of PTZ treatment. The amounts of gamma2L and gamma2S subunit mRNAs were significantly increased in the hippocampus and cerebral cortex of kindled rats 3 and 30 days after treatment discontinuation, compared with those observed in control rats, and these effects were prevented by the concomitant administration of the anticonvulsant abecarnil. In contrast, the amounts of alpha1 and beta2 subunit mRNAs in these two brain regions did not differ significantly between kindled and control rats. The abundance of alpha1, beta2, gamma2L and gamma2S subunit mRNAs was decreased in the septum of rats 3 or 30 days after discontinuation of treatment with PTZ either alone or in combination with abecarnil. The amounts of none of the four subunit mRNAs measured differed significantly between the striatum or frontal cortex of kindled rats and control rats 3 days after drug discontinuation. Immunohistochemical analysis with antibodies to choline acetyltransferase revealed a marked decrease in the number of cholinergic neurons in the septum of kindled rats 30 days after discontinuation of PTZ treatment; this effect was not prevented by the administration of abecarnil. These results suggest that long-term treatment with PTZ induces a loss of GABAA receptors in the septum. Copyright 1999 Published by Elsevier Science B.V.