Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism

S. Jamadar, E. E. DeVito, R. E. Jiantonio, S. A. Meda, M. C. Stevens, M. N. Potenza, J. H. Krystal, G. D. Pearlson

Research output: Contribution to journalArticle

Abstract

Rationale: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-d-aspartate (NMDA) receptor function. Objectives: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. Methods: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. Results: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. Conclusions: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.

Original languageEnglish (US)
Pages (from-to)129-140
Number of pages12
JournalPsychopharmacology
Volume222
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

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Memantine
Alcoholism
Magnetic Resonance Imaging
Placebos
Corpus Striatum
Impulsive Behavior
Gyrus Cinguli
Temporal Lobe
aspartic acid receptor

Keywords

  • fMRI
  • Genetic risk of alcoholism
  • Go/No-Go
  • Memantine
  • NMDA receptor antagonist
  • Response execution
  • Response inhibition

ASJC Scopus subject areas

  • Pharmacology

Cite this

Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism. / Jamadar, S.; DeVito, E. E.; Jiantonio, R. E.; Meda, S. A.; Stevens, M. C.; Potenza, M. N.; Krystal, J. H.; Pearlson, G. D.

In: Psychopharmacology, Vol. 222, No. 1, 07.2012, p. 129-140.

Research output: Contribution to journalArticle

Jamadar, S. ; DeVito, E. E. ; Jiantonio, R. E. ; Meda, S. A. ; Stevens, M. C. ; Potenza, M. N. ; Krystal, J. H. ; Pearlson, G. D. / Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism. In: Psychopharmacology. 2012 ; Vol. 222, No. 1. pp. 129-140.
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abstract = "Rationale: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-d-aspartate (NMDA) receptor function. Objectives: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. Methods: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. Results: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. Conclusions: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.",
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AU - Jamadar, S.

AU - DeVito, E. E.

AU - Jiantonio, R. E.

AU - Meda, S. A.

AU - Stevens, M. C.

AU - Potenza, M. N.

AU - Krystal, J. H.

AU - Pearlson, G. D.

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N2 - Rationale: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-d-aspartate (NMDA) receptor function. Objectives: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. Methods: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. Results: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. Conclusions: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.

AB - Rationale: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-d-aspartate (NMDA) receptor function. Objectives: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. Methods: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. Results: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. Conclusions: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.

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