title: Acute inhibition of mGluR5 disrupts behavioral flexibility.
abstract: 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.
authors.affiliation: Genetics Program, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Ferzin
authors.initials: F
authors.lastname: Sethna
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States; Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States. Electronic address: wangho@su.edu.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D003463:Cues; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; C121465:6-methyl-2-(phenylethynyl)pyridine
keywords: Contextual fear memory; Extinction; MPEP; PTSD; Spatial memory; mGluR5