ABSENCE OF MODIFICATIONS OF THE PHARMACOLOGICAL PROPERTIES OF THE GABA(A) RECEPTOR COMPLEX DURING AGING, AS ASSESSED IN 3-MONTH-OLD AND 24-MONTH-OLD RAT CEREBRAL-CORTEX

We have investigated the possible modifications of the pharmacological properties of Type I and Type II benzodiazepine binding sites of the gamma-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 [H-3]zolpidem (a Type I-specific ligand) or [H-3]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 [H-3]flunitrazepam binding in aged cortical membranes from Wistar rats. Furthermore, the [H-3]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 [H-3]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.