AGING RELATED ALTERATIONS IN GABA-A RECEPTOR SUBUNIT MESSENGER-RNA LEVELS IN FISCHER RATS

The influence of aging on the binding of ligands to picrotoxin binding sites as well as steady state levels of mRNA for various alpha-subunits of gamma-aminobutyric acid (GABA) receptor complex was investigated in male Fischer F-344 rats. In aged rats, the binding of [S-35]t-butyl-bicyclophosphorothionate (TBPS) was significantly reduced. This decrease in TBPS binding derived from a reduced density of binding sites, rather than from affinity changes, in both cerebral cortex and cerebellum. In aged rats, alpha-1 mRNA level decreased approximately 70% between age 6 months and 24 months in the cerebral cortex (P < 0.005). In contrast, alpha-1 mRNA remained unchanged in the cerebellum of old rats. The association of a decrease in picrotoxin binding sites in the cerebral cortex with a decline in alpha-1 mRNA level in the cerebral cortex and in alpha-2 mRNA level in the cerebellum is indicated. Alpha-6 mRNA level increased with age in the cerebellum. These findings indicate a selective age related modulation in the stoichiometry of GABA(A) receptor in aging.