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

• Published in: Psychopharmacologia 2012-07, Vol.222 (1), p.129-140
• Main Authors: Jamadar, S., DeVito, E. E., Jiantonio, R. E., Meda, S. A., Stevens, M. C., Potenza, M. N., Krystal, J. H., Pearlson, G. D.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Alcoholism; Alcoholism - epidemiology; Alcoholism and acute alcohol poisoning; Antagonist drugs; Aspartate; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Caudate Nucleus - metabolism; Double-Blind Method; Drug abuse; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Family Health; Female; Functional magnetic resonance imaging; Genetics; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Gyrus Cinguli - metabolism; Humans; impulsive behavior; Impulsive Behavior - epidemiology; Inhibition (Psychology); Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical sciences; memantine; Memantine - administration & dosage; Memantine - pharmacology; Methyl aspartate; N-Methyl-D-aspartic acid receptors; Nervous system agents; Neuropharmacology; Neurosciences; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Reaction time task; Receptor mechanisms; Toxicology; Young Adult
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2628-2

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.