Modest reduction of benzodiazepine binding in rat brain in vivo induced by antisense oligonucleotide to GABA A receptor γ 2 subunit subtype

Abstract

The GABA A (γ-aminobutyric acid-A) receptor γ 2 subunit subtype is functionally integral part of the benzodiazepine binding site of the GABA A 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 GABA A receptor γ 2 subinit subtype. Intracerebroventricular infusions of an antisense oligonucleotide reduced benzodiazepine receptor radioligand binding by 9–15% in specific rat brain regions.