Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP).
OBJECTIVE
The amplitude of the cortically generated auditory event-related potential (ERP) components P1 and N1 decreases as the interval between successive stimuli (ISI) decreases. Although the phenomenon of P1 and N1 refractoriness is well established, the underlying mechanisms are poorly understood. The present study investigates P1 and N1 refractoriness in the awake monkey in order to investigate underlying mechanisms.


METHODS
Auditory ERP were obtained in response to repetitive auditory stimuli presented at 5 levels of ISI between 150 ms and 9 s, prior to and following administration of the selective N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP).


RESULTS
P1 and N1 amplitude declined in monkeys with decreasing ISI, with similar temporal characteristics to that observed in humans. PCP inhibited P1 and N1 generation at long, but not short, ISI producing a pattern similar to that recently observed in schizophrenic subjects.


CONCLUSIONS
The present findings suggest that the primate P1/N1 model may be useful for investigating mechanisms underlying impaired information processing in schizophrenia, and that NMDA receptor dysfunction may play a key role in information processing dysfunction associated with schizophrenia.
Javitt
D C
DC
Program in Cognitive Neuroscience and Schizophrenia, The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, USA. javitt@nki.rfmh.org
Jayachandra
M
M
Lindsley
R W
RW
Specht
C M
CM
Schroeder
C E
CE
D000161:Acoustic Stimulation; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology; D006801:Humans; D008252:Macaca fascicularis; D008959:Models, Neurological; D010622:Phencyclidine / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D010622:Phencyclidine