| First Author | Kash SF | Year | 1999 |
| Journal | Proc Natl Acad Sci U S A | Volume | 96 |
| Issue | 4 | Pages | 1698-703 |
| PubMed ID | 9990087 | Mgi Jnum | J:53060 |
| Mgi Id | MGI:1331245 | Doi | 10.1073/pnas.96.4.1698 |
| Citation | Kash SF, et al. (1999) Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci U S A 96(4):1698-703 |
| abstractText | The larger isoform of the enzyme glutamate decarboxylase, GAD67, synthesizes >90% of basal levels of gamma-aminobutyric acid (GABA) in the brain. In contrast, the smaller isoform, GAD65, has been implicated in the fine-tuning of inhibitory neurotransmission. Mice deficient in GAD65 exhibit increased anxiety-like responses in both the open field and elevated zero maze assays. Additionally, GAD65-deficient mice have a diminished response to the anxiolytics diazepam and pentobarbital, both of which interact with GABA-A receptors in a GABA-dependent fashion to facilitate GABAergic neurotransmission. Loss of GAD65-generated GABA does not appear to result in compensatory postsynaptic GABA-A receptor changes based on radioligand receptor binding studies, which revealed no change in the postsynaptic GABA-A receptor density. Furthermore, mutant and wild-type animals do not differ in their behavioral response to muscimol, which acts independently of the presence of GABA. We propose that stress-induced GABA release is impaired in GAD65-deficient mice, resulting in increased anxiety-like responses and a diminished response to the acute effects of drugs that facilitate the actions of released GABA. |
