title: Nonhuman primate model of schizophrenia using a noninvasive EEG method.
abstract: There is growing evidence that impaired sensory-processing significantly contributes to the cognitive deficits found in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are reduced in schizophrenia patients and may be used as biomarkers of the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine, elicit many symptoms of schizophrenia when administered to normal subjects, including reductions in the MMN and the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade using subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were directly comparable to those recorded from humans. We first developed methods that allowed recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs during an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, as well as in normal subjects given ketamine, we observed a significant decrease in amplitude of both ERPs. Our findings suggest the potential of a pharmacologically induced model of schizophrenia in NHPs that can pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermore, given the established link between these ERPs, the glutamatergic system, and deficits in other neuropsychiatric disorders, our model can be used to investigate a wide range of pathologies.
authors: Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037.
authors: Ricardo
authors: R
authors: Gil-da-Costa
authors: Gene R
authors: GR
authors: Stoner
authors: Raynard
authors: R
authors: Fung
authors: Thomas D
authors: TD
authors: Albright
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000502:physiology*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: brain; medicine; monkey; neurology; psychiatry
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