EFFECTS OF CHRONIC ETHANOL ADMINISTRATION ON [H-3] ZOLPIDEM BINDING IN RAT-BRAIN

The effect of chronic ethanol administration on [H-3]zolpidem binding was measured in rat brain. [H-3]Zolpidem selectively labels gamma-aminobutyric acid(A)-benzodiazepine type 1 receptors, which are highly correlated with ethanol-sensitive gamma-aminobutyric acid (GABA) responses in brain. Recombinant expression studies have suggested that this GABA(A) receptor subtype requires the expression of alpha(1) subunits and is not selectively labeled by classic GABAergic ligands. Since chronic ethanol administration reduces alpha(1) subunit mRNA and polypeptide levels, we investigated whether alterations in [H-3]zolpidem binding would also be detected. Chronic ethanol administration did not reduce [H-3]zolpidem binding. Instead small, but reproducible, increases in [H-3]zolpidem binding density were detected in cortex and cerebellum with no change in affinity. No alterations in [H-3]zolpidem binding to striatum and hippocampus were observed. These findings suggest that chronic ethanol administration may have differential effects on [H-3]zolpidem binding sites and alpha(1) subunit expression. Alterations in alpha(1) subunit expression following chronic ethanol administration may involve other GABA(A) receptor subtypes or high affinity [H-3]zolpidem binding may be dependent on the expression of additional GABA(A) receptor subunits.