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Psychopharmacology (2012) 222:129140 DOI 10.1007/s00213-011-2628-2
ORIGINAL INVESTIGATION
Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activityin 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
Received: 31 May 2011 /Accepted: 19 December 2011 /Published online: 4 February 2012 # Springer-Verlag 2012
AbstractRationale 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-striatalparietal 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.
Keywords Memantine . Genetic risk of alcoholism . Go/No-Go . NMDA receptor antagonist . fMRI . Response inhibition . Response execution
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00213-011-2628-2
Web End =10.1007/s00213-011-2628-2 ) contains supplementary material, which is available to authorized users.
S. Jamadar (*) : R. E. Jiantonio : S. A. Meda : M. C. Stevens :
G. D. PearlsonOlin Neuropsychiatry Research Center, Institute of Living, Hartford, CT 06106, USAe-mail: [email protected]
E. E. DeVito : M. C. Stevens : M. N. Potenza : J. H. Krystal :
G. D. PearlsonDepartment of Psychiatry, Yale University, New Haven, CT, USA
M. N. Potenza...