Age-related alterations in GABA(A) receptor subunits in the nonhuman primate hippocampus

Pharmacological studies have documented that altered drug responses, particularly to benzodiazepines, are common in elderly populations. While numerous factors may contribute to changes in drug response, age-related alterations in the molecular composition of GABA(A) receptors may be a key factor in regulating these responses. We employed quantitative densitometry to examine the cytological features and density of highly prevalent hippocampal GABA(A) receptor subunits (alpha1 and beta2/3) in young and aged rhesus monkeys. alpha1 and beta2/3 subunit immunostaining was differentially distributed throughout the hippocampus. In addition, beta2/3 immunolabeling in aged monkeys was characterized by marked intersubject variability in labeling intensity, with dramatic reductions present in 3 of 5 samples. alpha1 immunolabeling in aged monkeys was significantly reduced in the CA2 and CA3 subregions, and in hilus/polymorphic layer of the dentate gyrus. Collectively, our findings demonstrate that not only are GABA(A) receptor subunits differentially distributed throughout the hippocampus, but they are also differentially altered with increased age--changes that may have an important impact on the binding properties of GABA(A) receptor pharmacological agents.