Modest reduction of benzodiazepine binding in rat brain in vivo induced by antisense oligonucleotide to GABAA receptor gamma 2 subunit subtype.

The GABAA (gamma-aminobutyric acid-A) receptor gamma 2 subunit subtype is probably a functionally integral part of the benzodiazepine binding site of the GABAA receptor complex, important for benzodiazepine pharmacology. We have evaluated the possibility of specifically reducing benzodiazepine receptor binding properties in vivo using phosphorothioate antisense oligodeoxynucleotides to inhibit the expression of GABAA receptor gamma 2 subunit subtype. Intracerebroventricular infusions of an antisense oligonucleotide reduced benzodiazepine receptor radioligand binding by 9-15% in specific rat brain regions.