Models of schizophrenia in humans and animals based on inhibition of NMDA receptors.
Věra Bubeníková-valešová, Jiří Horáček, Monika Vrajová, Cyril Höschl
Neuroscience and biobehavioral reviews July 1, 2008 DOI: 10.1016/j.neubiorev.2008.03.012 via PubMed
Summary
AI-generated from the abstractResearch 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.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Key finding | NMDA receptor antagonist models in humans and rats show phenomenological validity for schizophrenia research, and the neurodevelopmental model suggests early-life glutamatergic dysfunction may underlie later psychosis. |
Abstract
The research of the glutamatergic system in schizophrenia has advanced with the use of non-competitive antagonists of glutamate NMDA receptors (phencyclidine, ketamine, and dizocilpine), which change both human and animal behaviour and induce schizophrenia-like manifestations. Models based on both acute and chronic administration of these substances in humans and rats show phenomenological validity and are suitable for searching for new substances with antipsychotic effects. Nevertheless, pathophysiology of schizophrenia remains unexplained. In the light of the neurodevelopmental model of schizophrenia based on early administration of NMDA receptor antagonists it seems that increased cellular destruction by apoptosis or changes in function of glutamatergic NMDA receptors in the early development of central nervous system are decisive for subsequent development of psychosis, which often does not manifest itself until adulthood. Chronic administration of antagonists initializes a number of adaptation mechanisms, which correlate with findings obtained in patients with schizophrenia; therefore, this model is also suitable for research into pathophysiology of this disease.