Effects of memantine on event-related potential, oscillations, and complexity in individuals with and without family histories of alcoholism.

Abstract

Enhanced N-methyl-D-aspartate (NMDA) receptor function associated with a positive family history of alcoholism (FHP) has been hypothesized to contribute to the heritable risk for alcoholism. The objective of this study was to evaluate the relationship of alcoholism family history, NMDA receptor function, and cortical information processing by testing acute effects of the NMDA receptor antagonist memantine on event-related potential (ERP). Twenty-two healthy FHP and 20 healthy family history-negative (FHN; no alcoholic relatives) subjects were administered placebo or 40 mg of memantine under double-blind counterbalanced conditions on two separate occasions. Electroencephalogram data were collected from eight channels with eyes open during an auditory oddball discrimination task. We evaluated P3b amplitude, total theta, alpha activity, and fractal dimension from ERP trials. FHP and FHN subjects did not differ in P3b amplitude. A significant Group × Drug interaction was observed in theta, alpha activity, and fractal dimension at the parietal and occipital sites. FHP individuals exhibited significantly higher fractal dimension and lower theta and alpha activity after placebo relative to FHN subjects. Following memantine administration, theta activity decreased in both groups but more markedly for FHN individuals. Alpha activity decreased for FHN subjects and increased for FHP individuals, whereas the fractal dimension decreased for FHP subjects and increased for FHN subjects after memantine. A plausible interpretation of these results is that FHP individuals may have altered NMDA receptor function compared with FHN individuals. These findings provide additional evidence of differences in the regulation of NMDA receptor function between FHP and FHN individuals.