Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Open accessAbstract
Background Auditory mismatch negativity (MMN) and P300 event-related potentials (ERPs) are reduced in schizophrenia patients and healthy volunteers administered the N-methyl-D-aspartate glutamate receptor antagonist, ketamine. In rodents, N-acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of N-methyl-D-aspartate receptor antagonists. On the basis of these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans.Methods This randomized, double-blind, placebo-controlled study consisted of 2 test days during which subjects (n = 16) were administered oral NAC (3000 mg in divided doses) or matching placebo 165 min before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Behavioral and ERP data including auditory MMN and P300 were collected during each test day.Results Ketamine produced psychotic-like positive symptoms, reductions in working memory and sustained attention performance, and amplitude reductions for the frequency- and intensity-deviant MMNs and P300. NAC pretreatment did not reduce the behavioral or ERP effects of ketamine. In addition, NAC reduced frequency-deviant MMN amplitude and increased target and novelty P3 amplitudes. The decrements in frequency-deviant MMN amplitude produced by ketamine and NAC were not additive.Conclusions NAC did not attenuate the effects of ketamine in humans, in contrast to previous studies in animals. NAC merits further investigation as a cognitive enhancing agent due to its ability to increase the P300 amplitude.
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N-acetylcysteine pretreatment in healthy subjects with ketamine-induced psychosis did not reduce the effect of ketamine on cognition.
“However, NAC pretreatment in healthy subjects with ketamine-induced psychosis did not reduce the effect of ketamine on cognition [159].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [159]
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- Authors
- Gunduz-Bruce, H., Reinhart, R. M. G., Roach, B. J., Gueorguieva, R., Oliver, S., D'Souza, D. C., Ford, J. M., Krystal, J. H., & Mathalon, D. H.
- Affiliations
- Vanderbilt University (US)
- University of California, San Francisco (US)
- Yale University (US)
- San Francisco VA Medical Center (US)
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 71
- Issue
- 11
- Pages
- 969-977
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3290754
- OpenAlex
- W2017825692
- Cited by
- 93
- References
- 76
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 5 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 58262, MH067967, MH40052)
- National Institute on Alcohol Abuse and Alcoholism (2P50 AA 012870, K05 AA 14906)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- N-acetylcysteine, ketamine, NMDA receptor antagonism, mismatch negativity, P300, event-related potentials, glutamate modulation, schizophrenia, working memory, sustained attention, cognitive enhancement, novelty P3
- MeSH terms
- Acetylcysteine, Adult, Behavior, Cognition, Electroencephalography, Evoked Potentials, Auditory, Female, Humans, Ketamine, Male, Memory, Psychomotor Performance, Reaction Time, Schizophrenia, Free Radical Scavengers, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Event-Related Potentials, P300
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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