Archival ReportChronic Metabotropic Glutamate Receptor 5 Inhibition Corrects Local Alterations of Brain Activity and Improves Cognitive Performance in Fragile X Mice
Section snippets
Mice
Fmr1 KO mice (19) were obtained from Jackson Laboratories(Bar Harbor, Maine) and maintained on a congenic C57BL/6J background. All animal work was approved by local Swiss veterinary authority, and all experiments were conducted with experimenters blind to genotype and drug treatment.
Drugs and Treatment
CTEP, MPEP, and [3H]-ABP688 were synthesized at F. Hoffmann-La Roche AG (Basel, Switzerland) CTEP was formulated as microsuspension in vehicle (.9 % sodium chloride, .3 % Tween-80). Chronic treatment started at the
Correction of Learning Deficit in the Inhibitory Avoidance and Extinction Task
Cognitive deficits are a core symptom of FXS, which is reproduced in Fmr1 KO mice (2). In agreement with previous results 6, 23, 24, Fmr1 KO mice exhibited a robust deficit in the acquisition of the IAE task. The latency to enter the dark compartment was significantly reduced in vehicle-treated Fmr1 KO mice compared with WT littermates 6 hours after conditioning (p = .042; Figure 1C,D). This deficit persisted at the 24-hour test session after one (p = .048) but not two (p = .14) extinction
Discussion
The current study examined for the first time the alterations in brain activity patterns in a vertebrate model of fragile X with and without chronic pharmacologic inhibition of mGlu5, employing fMRI in Fmr1 KO and WT mice. In addition, principal component regression was explored as a means to extract interrelationships between brain activity patterns and learning or extinction capacities. Furthermore, mGlu5 expression levels were quantified across numerous brain areas in both genotypes.
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