GRM2 and schizophrenia: The mGlu2-centric scenario in the treatment of schizophrenia is supported by a large number of preclinical studies showing that the behavioral effects of orthosteric mGlu2/3 receptor agonists in behavioral tests that are predictive of antipsychotic activity are abrogated in mGlu2 receptor knockout mice, and that selective mGlu2 receptor PAMs display robust antipsychotic-like activity in rodents (Gerwirtz and Marek, 2000; Schoepp and Marek, 2002; Egan et al., 2004; Benneyworth et al., 2007; Patil et al., 2007; Conn et al., 2008).