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Cognition and behavior: Fragile X treatment has ill effects

A compound that shows promise as a treatment for fragile X syndrome alleviates repetitive behaviors in mice, but unexpectedly makes them less social.

By Jessica Wright

2 September 2011 | 2 min read

This article is more than five years old.

Neuroscience—and science in general—is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

A compound that shows promise as a treatment for fragile X syndrome alleviates repetitive behaviors in mice, but unexpectedly makes them less social, according to a study published 5 August in Brain Research¹.

The compound, MPEP, inactivates mGluR5, a receptor for chemical messengers that regulate excitatory signaling. Because mGluR5 activates many of the same molecules as the fragile X protein, FMRP, researchers are testing inhibitors of mGluR5 as therapies for fragile X syndrome and, potentially, autism.

A 2010 study shows that MPEP treatment alleviates repetitive behaviors in BTBR mice, an inbred strain that mimics many of the core symptoms of autism². Another study published in June shows that MPEP also lessens repetitive behaviors and seizures in mouse models of fragile X syndrome³.

In the new study, researchers looked at the effect of MPEP treatment on BALB/c mice, an inbred strain that is less social than typical Swiss Webster mice. Treatment with MPEP has no effect on how long BALB/c mice spend in a chamber containing a novel mouse compared with one that contains an object. However, while in that chamber, BALB/c mice treated with MPEP spend more of their time sniffing and exploring the novel mouse than when treated with placebo, the study found.

By contrast, Swiss Webster mice treated with MPEP spend less time sniffing a novel mouse than those treated with placebo. MPEP also lessens the number of times these mice approach a novel mouse when allowed to interact freely.

Still, confirming results from previous studies, MPEP significantly decreases the amount of time that Swiss Webster mice engage in repetitive behaviors when placed in a cage with a freely roaming mouse, such as rearing up, climbing the walls of the cage and self-grooming.

Compared with Swiss Webster mice, BALB/c mice have low levels of each of these repetitive behaviors in the presence of another mouse, and these behaviors are not significantly affected by MPEP treatment.