Abstract
The influence of aging on the binding of ligands to picrotoxin binding sites as well as steady state levels of mRNA for various α subunits of γ-aminobutyric acid (GABA) receptor complex was investigated in male Fischer F-344 rats. In aged rats, the binding of [ 35 S]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, α 1 mRNA level decreased approximately 70% between age 6 months and 24 months in the cerebral cortex ( P < 0.005). In contrast, α 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 α 1 mRNA level in the cerebral cortex and in α 2 mRNA level in the cerebellum is indicated. α 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.
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