Absence of modifications of the pharmacological properties of the GABA A receptor complex during aging, as assessed in 3- and 24-month-old rat cerebral cortex

Abstract

We have investigated the possible modifications of the pharmacological properties of Type I and Type II benzodiazepine binding sites of the γ-aminobutyric acid A (GABA A) receptor complex in cortical membranes from 3- and 24-month-old Wistar or Fischer rats. No major changes were found in the binding parameters of [ 3H]zolpidem (a Type I-specific ligand) or [ 3H]flunitrazepam (a non-selective benzodiazepine). Neither the K d values nor the B max for either ligand were modified during aging in cortical membranes from Wistar or Fischer rats. Consequently, the proportion of Type I binding sites was also unmodified in aged cortical membranes. The absence of modifications of Type I and Type II binding sites was also confirmed by Cl 218,872 displacement of [ 3H]flunitrazepam binding in aged cortical membranes from Wistar rats. Furthermore, the [ 3H]muscimol binding and the allosteric interactions between Type I or total benzodiazepine binding sites and GABA binding sites also remained unaltered with aging in cortical membranes from Wistar rats. Moreover, the pattern and proportion of the [ 3H]flunitrazepam photoaffinity labeled peptides were also unmodified by aging. These results demonstrate the absence of modifications in Type I or total benzodiazepine binding sites of the GABA A receptor complex from adult and aged cortical membranes in Fischer or Wistar rats.