title: Models of schizophrenia in humans and animals based on inhibition of NMDA receptors.
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.
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic. bubenikova@pcp.lf3.cuni.cz
authors.forename: Vera
authors.initials: V
authors.lastname: Bubeníková-Valesová
authors.forename: Jirí
authors.initials: J
authors.lastname: Horácek
authors.forename: Monika
authors.initials: M
authors.lastname: Vrajová
authors.forename: Cyril
authors.initials: C
authors.lastname: Höschl
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008959:Models, Neurological; D011605:Psychoses, Substance-Induced / Q000378:metabolism / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine