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


OBJECTIVE
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.
Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT 06106, USA. sjamadar@harthosp.org
S
S
Jamadar
E E
EE
DeVito
R E
RE
Jiantonio
S A
SA
Meda
M C
MC
Stevens
M N
MN
Potenza
J H
JH
Krystal
G D
GD
Pearlson
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology*; D002421:Caudate Nucleus / Q000378:metabolism; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005192:Family Health; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007175:Impulsive Behavior / Q000453:epidemiology; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine