Modest reduction of benzodiazepine binding in rat brain in vivo induced by antisense oligonucleotide to GABAA receptor γ2 subunit subtype

Abstract

The GABA_A (γ-aminobutyric acid-A) receptor γ₂ 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 γ₂ subinit subtype. Intracerebroventricular infusions of an antisense oligonucleotide reduced benzodiazepine receptor radioligand binding by 9–15% in specific rat brain regions.