The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating, Food-Seeking Behavior and Compulsive Eating: Role of the Nucleus Accumbens Shell (2014)

Neuropsychopharmacology. 2014 Nov 10. doi: 10.1038/npp.2014.299. [Epub ahead of print]

Smith KL1, Rao RR1, Velázquez-Sánchez C1, Valenza M1, Giuliano C2, Everitt BJ2, Sabino V1, Cottone P1.


Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic NMDA receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist memantine on palatable food-induced behavioral adaptations using a rat model which mimics the characteristic symptomatology observed in binge eating disorder. For this purpose, we allowed male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding, we tested the effects of memantine on Chow and Palatable food groups’ intake. Then, we tested the effects of memantine on food seeking behavior, under a second order schedule of reinforcement. Furthermore, we investigated the effects of memantine on the intake of food when it was offered in an aversive, bright compartment of a light/dark conflict test. Finally, we evaluated the effects of memantine on FR1 responding for food, when microinfused into the nucleus accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like eating and fully blocked food seeking behavior and compulsive eating, selectively in the Palatable food group. The drug treatment did not affect performance of control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion of memantine decreased binge-like eating. Together, these findings substantiate a role of memantine as a potential pharmacological treatment for binge eating disorder.Neuropsychopharmacology accepted article preview online, 10 November 2014. doi:10.1038/npp.2014.299.