Pharmacological enhancement of mGluR5 facilitates contextual fear memory extinction

Behavioral exposure therapy, which involves extinction of the previously acquired fear, has been used to treat anxiety-related symptoms such as post-traumatic stress disorder. It has been hypothesized that proextinction pharmacotherapeutics may enhance the efficacy of exposure therapy. Systemic administration of the metabotropic glutamate receptor 5 (mGluR5)-positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) facilitated the extinction of contextual fear memory. Notably, CDPPB also enhanced the initial fear memory formation, and had no effect on memory retrieval. Our data suggest that positive regulation of mGluR5 may offer a new method to enhance exposure therapy through facilitating extinction without adversely affecting other aspects of memory process.