Memantine reduces consumption of highly palatable food in a rat model of binge eating

Abstract

Excessive consumption of highly palatable food has been linked to the development of eating disorders and obesity, and can be modeled in non-food-deprived rats by offering them a limited (2-h daily) access to an optional dietary fat. Since the glutamatergic system has recently emerged as a viable target for binge-eating medication development, we compared the effects of subchronic treatment with glutamatergic receptor antagonists to the effects of a reference appetite-suppressing agent sibutramine on highly palatable food (lard) and normal chow intake. In three separate experiments, the consumption of a standard laboratory chow and lard were measured during 12 days of medication treatment and for 6 days afterwards. Generalized estimating equations analysis demonstrated that sibutramine (7.5 mg/kg, p.o.) significantly decreased lard consumption, with a concurrent increase in chow consumption. Sibutramine effects disappeared after treatment discontinuation. The NMDA receptor antagonist memantine (5 mg/kg, i.p.) significantly decreased lard consumption and increased chow consumption, comparable to effects of sibutramine; however, memantine's effects persisted after treatment discontinuation. The effects of the mGluR5 antagonist MTEP (7.5 mg/kg, i.p.) on food consumption were in the same direction as seen with memantine, but the observed differences were not significant. In an additional control experiment, sibutramine and memantine reduced unlimited (24 h) chow intake during the treatment phase. Present results provide evidence that glutamatergic neurotransmission might be involved in the regulation of excessive consumption of highly palatable foods, and suggest that NMDA receptor may be an attractive target for developing obesity and disordered eating pharmacotherapies.

Fig. 1

2-h consumption of lard and chow at baseline, during repeated treatment with sibutramine (a), memantine (b) or MTEP (c), and during post-treatment phase. The group means, the GEE-fitted lines, and the p value for between-group differences (medication vs. vehicle control) are shown. Number of animals in each group N = 9 a, N = 10 b, N = 8 c

Fig. 2

24-h consumption of unlimited access chow at baseline, during repeated treatment with sibutramine, memantine, or MTEP and during post-treatment phase. Figure shows the group means ± SEM and the GEE-fitted lines: solid, dotted, dash-dotted and dashed for vehicle, sibutramine, memantine and MTEP, respectively. Number of animals in each group was 12–13

Fig. 3

Body weight of all the groups tested. Panels show group means ± SEM. Panels 1–3 represents rats that were offered a limited access to the lard since the beginning of the experiment and were treated with respective medications during the treatment phase. Panel 4 represents rats that had continuous access to chow but no access to lard