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

Sharna Jamadar, Elise E DeVito, Rachel E Jiantonio-Kelly, Shashwath A Meda, Michael C Stevens, Marc Nicholas Potenza, John Harrison Krystal, Godfrey D Pearlson

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

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
Pages (from-to)129 - 140
Number of pages12
JournalPsychopharmacology
Volume222
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

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