The uncompetitive NMDA receptor antagonist memantine blocks compulsive eating of palatable food

Abstract

Binge-eating disorder is one of the most prevalent illnesses in the U.S. today and is characterized by short periods of excessive consumption of palatable food. Our study sought to explore the role of the glutamatergic system, one of the key neural pathways associated with reward-related learning and motivation, in binge-eating. We trained male rats to consume either a highly palatable diet or a standard chow diet within a limited time frame (1 hr/day) on a fixed ratio 1 (FR1) schedule of reinforcement. The palatable- fed rats quickly developed “bingeing” behavior and exhibited compulsive eating and risk- taking behavior when faced with an aversive environment. We evaluated the effects of systemic administration of the uncompetitive NMDA receptor antagonists, ketamine and memantine, and found that memantine significantly decreased FR1 responding and compulsive eating of palatable food, but not chow, and reduced the difference in risk- taking behavior between the palatable-fed and chow-fed groups. Site-specific injections of memantine into the nucleus accumbens, a key region of reward processing, also decreased responding for food selectively in the bingeing rats. These findings, taken together, implicate the glutamatergic system within the mesolimbic reward pathway in modulating neuroadaptive mechanisms that lead to the development of binge-eating disorder and suggest a potential pharmacological strategy to combat this debilitating disease.