Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase

摘要: The larger isoform of the enzyme glutamate decarboxylase, GAD67, synthesizes >90% basal levels γ-aminobutyric acid (GABA) in brain. In contrast, smaller isoform, GAD65, has been implicated fine-tuning inhibitory neurotransmission. Mice deficient GAD65 exhibit increased anxiety-like responses both open field and elevated zero maze assays. Additionally, GAD65-deficient mice have a diminished response to anxiolytics diazepam pentobarbital, which interact with GABA-A receptors GABA-dependent fashion facilitate GABAergic Loss GAD65-generated GABA does not appear result compensatory postsynaptic receptor changes based on radioligand binding studies, revealed no change density. Furthermore, mutant wild-type animals do differ their behavioral muscimol, acts independently presence GABA. We propose that stress-induced release is impaired mice, resulting acute effects drugs actions released