Title
Pharmacological treatment of fragile X syndrome with GABAergic drugs in a knockout mouse modelPharmacological treatment of fragile X syndrome with GABAergic drugs in a knockout mouse model
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Human molecular genetics
Neurochemistry and behaviour
Cognitive Genetics (COGNET)
Publication type
article
Publication
Amsterdam,
Subject
Psychology
Biology
Human medicine
Source (journal)
Behavioural brain research. - Amsterdam
Volume/pages
229(2012):1, p. 244-249
ISSN
0166-4328
ISI
000302047600030
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Molecular and electrophysiological studies have provided evidence for a general downregulation of the GABAergic system in the Fmr1 knockout mouse. GABAA receptors are the main inhibitory receptors in the brain and the GABAA receptor was proposed as a novel target for treatment of the fragile X syndrome, the most frequent form of intellectual disability. This study examined the functionality of the GABAA receptor in rotarod and elevated plus maze tests with fragile X mice treated with GABAA receptor agonists, the benzodiazepine diazepam and the neuroactive steroid alphaxalone. In addition, the effect of GABAA receptor activation on the audiogenic seizure activity was determined. We proved that the GABAA receptor is still sensitive to GABAergic drugs as the sedative effect of diazepam resulted in a decreased latency time on the rotarod and alphaxalone had a clear anxiolytic effect in the elevated plus maze, decreasing the frequency of entries, the total time spent and the path length in the closed arms. We also observed that treatment with ganaxolone could rescue audiogenic seizures in Fmr1 knockout mice. These findings support the hypothesis that the GABAA receptor is a potential therapeutic target for fragile X syndrome.
E-info
https://repository.uantwerpen.be/docman/iruaauth/bc85cc/bc73943f285.pdf
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