Models of schizophrenia in humans and animals based on inhibition of NMDA receptors.
Neuroscience and biobehavioral reviews July 1, 2008 Věra Bubeníková-valešová, Jiří Horáček, Monika Vrajová et al.
Research using non-competitive NMDA receptor antagonists—phencyclidine, ketamine, and dizocilpine—produces behavioral changes in humans and rats that resemble schizophrenia symptoms. Acute and chronic administration models show phenomenological validity and help test potential antipsychotic drugs. However, schizophrenia's pathophysiology remains unexplained. The neurodevelopmental model suggests that early-life NMDA receptor antagonism increases apoptosis or alters glutamatergic receptor function during central nervous system development, leading to psychosis that often emerges only in adulthood. Chronic antagonist administration triggers adaptation mechanisms that match findings in schizophrenia patients, making this model useful for studying the disease's pathophysiology.