Animal model of schizophrenia: dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine.
Annals of the New York Academy of Sciences November 1, 2006 Toshitaka Nabeshima, Akihiro Mouri, Rina Murai et al.
Repeated administration of phencyclidine (PCP) to mice produces behavioral deficits resembling the negative symptoms and cognitive impairments of schizophrenia, including increased immobility in a forced swimming test and impaired latent learning. These deficits persist after PCP withdrawal and are alleviated by atypical but not typical antipsychotics. PCP treatment reduces spontaneous glutamate levels and impairs NMDA receptor function in the prefrontal cortex, disrupting both pre- and postsynaptic glutamate transmission. Facilitation of NMDA receptor function with glycine-site agonists like D-cycloserine or glycine reverses the abnormal intracellular signaling and behavioral deficits. The findings suggest that disrupted NMDA receptor signaling underlies the emotional and cognitive deficits in this mouse model, which may be useful for studying antipsychotic effects.