Since mGlu5 can potentiate NMDAR responses in select rodent brain regions [77–79], it was initially proposed that mGlu5 PAMs were likely to exert their efficacy through potentiation of mGlu5-induced increases in NMDAR currents in forebrain regions implicated in the pathology of schizophrenia [72, 79]. This evidence concerns the gene GRM5 and schizophrenia.