Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder

Abstract

Excessive consumption of highly palatable foods may contribute to the development of weight gain. Therefore medications that selectively suppress eating of such foods would be useful in clinical practice. We compared the effects of the glutamatergic antagonists memantine and MTEP to dexfenfluramine in baboons given periodic access to highly palatable food and ad libitum access to a standard chow diet. Three days a week baboons received a sugar-coated candy during the first meal and standard standard-diet chow pellets were available in subsequent meals. All baboons derived a greater amount of energy from the single single-candy meal than from the standard diet across an entire day. Pre-treatment with dexfenfluramine, memantine, and MTEP produced decreases in candy consumption without altering candy-seeking behaviour. At the same time, dexfenfluramine and memantine, but not MTEP, produced a decrease in seeking and consumption of standard chow pellets. Both memantine and MTEP are promising agents for the treatment of obesity.

Figure 1

Diagram of experimental day. One candy meal followed by multiple food pellet meals were available on Monday, Wednesday and Friday, and only multiple food pellet meals were available on the remaining days of the week. A meal was initiated by the completion of a 30-min seeking interval during which every tenth response was followed by illumination of the lights that accompanied candy or food pellet delivery. Following the 30-min interval, every tenth response was followed by candy or food pellet delivery along with the light presentation. The taking component ended after the animal stopped responding for 10 min. In order to have another food pellet meal the animal had to gain complete the 30-min seeking interval. Thus timing and size of meals were determined individually by each animal.

Figure 2

Latency to the first candy meal (left panel) and the first food pellet meal (right panel) as a function of drug and dose. Error bars represent ±1 SEM. Error bars for the placebo values are based on all 4 placebo days.

Figure 3

Total number of candies earned during the single candy meal of each candy session (A) and total daily number of food pellets earned on pellet-only days (B) as a function of drug and dose. Error bars represent ±1 SEM. Error bars for the placebo values are based on all 4 placebo days.