title: Is the acute NMDA receptor hypofunction a valid model of schizophrenia?
abstract: Several genetic, neurodevelopmental, and pharmacological animal models of schizophrenia have been established. This short review examines the validity of one of the most used pharmacological model of the illness, ie, the acute administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In some cases, data on chronic or prenatal NMDA receptor antagonist exposure have been introduced for comparison. The face validity of acute NMDA receptor blockade is granted inasmuch as hyperlocomotion and stereotypies induced by phencyclidine, ketamine, and MK-801 are regarded as a surrogate for the positive symptoms of schizophrenia. In addition, the loss of parvalbumin-containing cells (which is one of the most compelling finding in postmortem schizophrenia brain) following NMDA receptor blockade adds construct validity to this model. However, the lack of changes in glutamic acid decarboxylase (GAD(67)) is at variance with human studies. It is possible that changes in GAD(67) are more reflective of the neurodevelopmental condition of schizophrenia. Finally, the model also has predictive validity, in that its behavioral and transmitter activation in rodents are responsive to antipsychotic treatment. Overall, although not devoid of drawbacks, the acute administration of NMDA receptor antagonists can be considered as a good model of schizophrenia bearing a satisfactory degree of validity.
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC (IDIBAPS), Carrer Rosselló 161, 6th floor, Room 630, E-08036 Barcelona, Spain. albert.adell@iibb.csic.es
authors.forename: Albert
authors.initials: A
authors.lastname: Adell
authors.forename: Laura
authors.initials: L
authors.lastname: Jiménez-Sánchez
authors.forename: Xavier
authors.initials: X
authors.lastname: López-Gil
authors.forename: Tamara
authors.initials: T
authors.lastname: Romón
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D010320:Parvalbumins / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*; D012377:Rodentia; D012559:Schizophrenia / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D010320:Parvalbumins; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D018698:Glutamic Acid; D007649:Ketamine; D010622:Phencyclidine; D004298:Dopamine