Phencyclidine and genetic animal models of schizophrenia developed in relation to the glutamate hypothesis.
Methods and findings in experimental and clinical pharmacology May 1, 2007 T Enomoto, Y Noda, T Nabeshima
The noncompetitive NMDA receptor antagonist phencyclidine (PCP) produces a schizophrenia-like psychosis in humans, including positive symptoms, negative symptoms, and cognitive dysfunction. PCP-treated animals show hyperlocomotion, social behavioral deficits, enhanced immobility in forced swimming, sensorimotor gating deficits, and cognitive dysfunctions, some of which persist after withdrawal from repeated treatment. Repeated PCP treatment also induces neurochemical and neuroanatomical changes. Genetic animal models based on the glutamate hypothesis of schizophrenia, such as NMDA receptor subunit knockdown or knockout mice, also exhibit schizophrenia-like behaviors. These PCP and genetic models are useful for evaluating novel therapeutic candidates and studying pathological mechanisms of schizophrenia.