EFFECTS OF CHRONIC PENTOBARBITAL TREATMENT ON THE GABA(A) RECEPTOR COMPLEX IN MAMMALIAN CORTICAL-NEURONS

In this study we examined the binding characteristics of the gamma-ami nobutyric acid (GABA(A)) receptor complex after chronic pentobarbital sodium treatment in cultured mammalian cortical neurons. Chronic panto barbital sodium treatment (200 mu M, 5 days) did not alter the basal b inding of ligands like [H-3]flunitrazepam, hyl-8-fluoro-5,6-dihydro-5- methyl-6-oxo-4H-imidazo [1,5 alpha][1,4]-BZ-3-carboxylate and thyl-8-a zido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5 alpha][1,4]BZ-3-carbox ylate that bind to the benzodiazepine (BZ) recognition site of the GAB A, receptor complex. Similarly, chronic pentobarbital sodium treatment did not alter the basal binding of [H-3]GABA and t-butylbicyclophosph oro[S-35]thionate. However, chronic pentobarbital sodium treatment pro duced uncoupling between GABA, barbiturate and neurosteroid sites with the BZ site. The efficacy (E(max)) values of GABA, pentobarbital and neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one, on [H-3]flunitrazepam binding were significantly decreased, whereas their potency (EC(50)) values were not altered after chronic pentobarbital sodium treatment. Taken together, these results suggest that chronic pentobarbital sodiu m treatment produces heterologous uncoupling of the GABA-BZ receptor i onophore complex.