Tags

Type your tag names separated by a space and hit enter

Glutamatergic modulation of auditory information processing in the human brain.
Biol Psychiatry 2012; 71(11):969-77BP

Abstract

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.

Authors+Show Affiliations

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. handan.gunduz-bruce@yale.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22036036

Citation

Gunduz-Bruce, Handan, et al. "Glutamatergic Modulation of Auditory Information Processing in the Human Brain." Biological Psychiatry, vol. 71, no. 11, 2012, pp. 969-77.
Gunduz-Bruce H, Reinhart RM, Roach BJ, et al. Glutamatergic modulation of auditory information processing in the human brain. Biol Psychiatry. 2012;71(11):969-77.
Gunduz-Bruce, H., Reinhart, R. M., Roach, B. J., Gueorguieva, R., Oliver, S., D'Souza, D. C., ... Mathalon, D. H. (2012). Glutamatergic modulation of auditory information processing in the human brain. Biological Psychiatry, 71(11), pp. 969-77. doi:10.1016/j.biopsych.2011.09.031.
Gunduz-Bruce H, et al. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biol Psychiatry. 2012 Jun 1;71(11):969-77. PubMed PMID: 22036036.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutamatergic modulation of auditory information processing in the human brain. AU - Gunduz-Bruce,Handan, AU - Reinhart,Robert M G, AU - Roach,Brian J, AU - Gueorguieva,Ralitza, AU - Oliver,Stephen, AU - D'Souza,Deepak C, AU - Ford,Judith M, AU - Krystal,John H, AU - Mathalon,Daniel H, Y1 - 2011/10/29/ PY - 2011/07/06/received PY - 2011/09/29/revised PY - 2011/09/30/accepted PY - 2011/11/1/entrez PY - 2011/11/1/pubmed PY - 2012/10/5/medline SP - 969 EP - 77 JF - Biological psychiatry JO - Biol. Psychiatry VL - 71 IS - 11 N2 - 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. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/22036036/Glutamatergic_modulation_of_auditory_information_processing_in_the_human_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(11)00952-8 DB - PRIME DP - Unbound Medicine ER -