LONG-LASTING REDUCTION OF INHIBITORY FUNCTION AND GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN A MODEL OF TEMPORAL-LOBE EPILEPSY

This study evaluated hippocampal inhibitory function and the level of expression of gamma-aminobutyric acid type A (GABA(A)) receptor mRNA i n an in vivo model of epilepsy, Chronic recurrent limbic seizures were induced in rats using injections of pilocarpine. Electrophysiological studies performed on hippocampal slices prepared from control and epi leptic animals 1 to 2 months after pilocarpine injections demonstrated a significant hyperexcitability in the epileptic animals, Reduced lev els of mRNA expression for the alpha 2 and alpha 5 subunits of the GAB A(A) receptors were evident in the CA1, CA2, and CA3 regions of the hi ppocampus of epileptic animals. No decrease in mRNA encoding alpha 1, beta 2, or gamma 2 GABA(A) receptor subunits was observed. In addition , no change in the mRNA levels of alpha CaM kinase II was seen. Select ive decreases in mRNA expression did not correlate with neuronal cell loss, The results indicate that selective, long-lasting reduction of G ABA(A) subunit mRNA expression and increased excitability, possibly re flecting loss of GABAergic inhibition, occur in an ill vivo model of p artial complex epilepsy.