Aging: Effect on the interaction of ethanol and pentobarbital with the benzodiazepine-GABA receptor-ionophore complex

Benzodiazepine receptor binding and modulation by pentobarbital and ethanol was studied using the detergent 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate to solubilize the γ-aminobutyric acid (GABA)-benzodiazepine receptor-ionophore complex from the brains of Fischer 344 rats of 3–4, 12–15 and more than 28 months of age. The affinity of the benzodiazepine binding site was significantly lower in the young rats compared to either the mature or senescent animals. However, no age-related changes in the maximum number of benzodiazepine binding sites or GABA concentrations occurred in the detergent extract. Pentobarbital produced practically identical dose-dependent enhancement of [ 3H]flunitrazepam specific binding in all 3 age groups. In contrast, ethanol between 0.1 and 200 mM failed to produce a dose-dependent effet on [ 3H]flunitrazepam specific binding in any age group. The effect of pentobarbital and ethanol on [ 35S]t-butyl-bicyclophosphorothionate ([ 35S]TBPS) specific binding to the picrotoxinin binding site was examined in the above solubilized receptor/ionophore complex under the same binding conditions. Both sedative-hypnotics produced a dose-dependent decrease in [ 35S]TBPS specific binding. However, pentobarbital was over 10,000 times more potent. It appears that ethanol may not enhance [ 3H]flunitrazepam specific binding in this solubilized preparation because of its weak action at the picrotoxinin binding site.