Acute inhibition of mGluR5 disrupts behavioral flexibility

Conditioned cues can sometimes elicit maladaptive responses as seen in the post-traumatic stress disorder (PTSD). Lack of effective fear extinction, which involves a process of inhibitory learning, is hypothesized to associate with PTSD. In this study, we tested the effect of acute pharmacological inhibition of mGluR5 activity on the extinction of fear memory and spatial memory. Intraperitoneal injection of the mGluR5 (metabotropic glutamate receptor 5) antagonist MPEP [2-Methyl-6-(phenylethynyl) pyridine hydrochloride] allowed the retrieval but prevented the extinction of contextual fear memory in mice. Without altering locomotor activity, MPEP inhibited the acquisition but not the consolidation of contextual fear memory. Further, administration of MPEP blocked the extinction of spatial memory in the Morris water maze paradigm. Our data suggest a necessary role of mGluR5 in regulating certain aspects of behavioral flexibility.