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 language | English (US) |
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Pages (from-to) | 129-140 |
Number of pages | 12 |
Journal | Psychopharmacology |
Volume | 222 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2012 |
Externally published | Yes |
Keywords
- Genetic risk of alcoholism
- Go/No-Go
- Memantine
- NMDA receptor antagonist
- Response execution
- Response inhibition
- fMRI
ASJC Scopus subject areas
- Pharmacology