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The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice

Content Provider	PubMed Central
Author	Veloz, M. F. Vinueza Buijsen, R. A. M. Willemsen, R. Cupido, A. Bosman, L. W. J. Koekkoek, S. K. E. Potters, J. W. Oostra, B. A. De Zeeuw, C. I.
Copyright Year	2012
Abstract	Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Patients with FXS do not only suffer from cognitive problems, but also from abnormalities/deficits in procedural memory formation. It has been proposed that a lack of fragile X mental retardation protein (FMRP) leads to altered long-term plasticity by deregulation of various translational processes at the synapses, and that part of these impairments might be rescued by the inhibition of type I metabotropic glutamate receptors (mGluRs). We recently developed the Erasmus Ladder, which allows us to test, without any invasive approaches, simultaneously, both procedural memory formation and avoidance behavior during unperturbed and perturbed locomotion in mice. Here, we investigated the impact of a potent and selective mGluR5 inhibitor (Fenobam) on the behavior of Fmr1 KO mice during the Erasmus Ladder task. Fmr1 KO mice showed deficits in associative motor learning as well as avoidance behavior, both of which were rescued by intraperitoneal administration of Fenobam. While the Fmr1 KO mice did benefit from the treatment, control littermates suffered from a significant negative side effect in that their motor learning skills, but not their avoidance behavior, were significantly affected. On the basis of these studies in the FXS animal model, it may be worthwhile to investigate the effects of mGluR inhibitors on both the cognitive functions and procedural skills in FXS patients. However, the use of mGluR inhibitors appears to be strongly contraindicated in healthy controls or non-FXS patients with intellectual disability.
Related Links	http://dx.doi.org/10.1111/j.1601-183x.2011.00763.x
Ending Page	331
Page Count	7
Starting Page	325
File Format	PDF
ISSN	16011848
e-ISSN	1601183X
Journal	Genes, Brain, and Behavior
Issue Number	3
Volume Number	11
Language	English
Publisher	Blackwell Publishing Ltd
Publisher Date	2012-04-01
Access Restriction	Open
Rights Holder	Blackwell Publishing Ltd
Subject Keyword	Genetics Behavioral Neuroscience Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neurology Genetics Behavioral Neuroscience

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