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

MF Vinueza Veloz, RAM Buijsen… - Genes, Brain and …, 2012 - Wiley Online Library
MF Vinueza Veloz, RAM Buijsen, R Willemsen, A Cupido, LWJ Bosman, SKE Koekkoek
Genes, Brain and Behavior, 2012Wiley Online Library
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 …
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.
Wiley Online Library