Pharmacologic characterization of GABAA/benzodiazepine receptor in rat hippocampus during aging

We have characterized the pharmacologic properties of the gamma-aminobutyric acid (GABAA)/benzodiazepine receptor complex in hippocampal membranes from 3-month- and 24-month-old Wistar rats. No major changes were found in [3H]flunitrazepam or [3H]muscimol binding parameters. Neither the dissociation constant(s) nor the Bmax for either ligand seemed to be modified during aging in hippocampus. Furthermore, the allosteric interaction between the barbiturates binding site and the GABA binding site, determined by pentobarbital stimulation of [3H] muscimol binding, remained unaltered. However, there was a significant increase with aging in the efficacy of the GABA-enhancement of [3H]flunitrazepam binding. On the other hand, we have also detected a significant increase in the proportion of type I benzodiazepine receptor in 24-month-old hippocampal membranes. We propose that the age-related increase in the efficacy of GABA-enhancement of [3H]flunitrazepam binding could be correlated with the increase in the proportion of type I benzodiazepine receptor. Based on these results it is tempting to speculate that the age-dependent modifications on the GABAA/benzodiazepine receptor might reflect an age-dependent neuronal degeneration of the hippocampus or the hippocampal formation.