In order to test the possible role of mGluR5 signaling in the behavioral endophenotypes of schizophrenia and other psychiatric disorders, we used genetic engineering to create mice carrying null mutations in this gene. Compared to their mGluR5 + / + littermates, mGluR5 À/À mice have disrupted latent inhibition (LI) as measured in a thirst-motivated conditioned emotional response procedure. Administration of the positive modulator of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR), CX546, during the conditioning phase only, improved the disrupted LI in mGluR5 knockout mice and facilitated LI in control C57BL/6J mice, given extended number of conditioning trails (four conditioning stimulus-unconditioned stimulus). Prepulse inhibition (PPI) was impaired in mGluR5 À/À mice to a level that could not be disrupted further by the antagonist of N-methyl-D-aspartate receptorsFMK-801. PPI deficit of mGluR5 À/À mice was effectively reversed by CX546, whereas aniracetam had a less pronounced effect. These data provide evidence that a potent positive AMPAR modulator can elicit antipsychotic action and represents a new approach for treatment of schizophrenia. Neuropsychopharmacology (2007) 32, 745-756.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.