Aging related alterations in GABA_A receptor subunit mRNA 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 α subunits of γ-aminobutyric acid (GABA) receptor complex was investigated in male Fischer F-344 rats. In aged rats, the binding of [³⁵S]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, α₁ mRNA level decreased approximately 70% between age 6 months and 24 months in the cerebral cortex (P < 0.005). In contrast, α₁ 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 α₁ mRNA level in the cerebral cortex and in α₂ mRNA level in the cerebellum is indicated. α₆ 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.