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, PO) 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, IP) 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, IP) 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.

Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

“…On the other hand, the administration of 2′-methoxyphenyl-(N-2′-pyridinyl)-p-fluorobenzamidoethyipiperazine (MPPF) (mGluR5 antagonist) results in a dose dependant reduction in cocaine self-administration [12,51]. This indicates that the mGluR5 receptor in AN may play a role in modulating a postsynaptic response to glutamate and dopamine [51,56] and thus has a net effect on disorders involved in pleasure seeking behaviour and pleasure sensation alterations. However, a binge pattern of drug consumption and binge eating may have similar regulatory mechanisms [56].…”

“…This indicates that the mGluR5 receptor in AN may play a role in modulating a postsynaptic response to glutamate and dopamine [51,56] and thus has a net effect on disorders involved in pleasure seeking behaviour and pleasure sensation alterations. However, a binge pattern of drug consumption and binge eating may have similar regulatory mechanisms [56].…”

“…The glutamatergic system has recently been a target for the development of binge-eating medication [57]. It was shown that memantine (a NMDA antagonist) and MTEP (a mGluR5 antagonist) reduces highly palatable food consumption in rats and baboons [56,60]. Memantine similarly reduced the effect of highly rewarding stimuli (e.g., sexual interaction and morphine intake) in mice [8,56].…”

“…It was shown that memantine (a NMDA antagonist) and MTEP (a mGluR5 antagonist) reduces highly palatable food consumption in rats and baboons [56,60]. Memantine similarly reduced the effect of highly rewarding stimuli (e.g., sexual interaction and morphine intake) in mice [8,56]. The density of mGluR5 alterations in the Hyp, ThV, cortical, raphe areas and brainstem found in the present study have been shown to be the brain regions implicated in the control of food intake and metabolism [8].…”

Genetic aspects of binge eating disorder Part 2. Molecular genetics and pharmacogenetic approaches

“…В экспериментальной модели был показан хороший эф-фект антагониста NMDA-рецепторов -мемантина, ко-торый в отличие от известного супрессора аппетита сибу-трамина продолжался после прекращения приема препа-рата. Это позволяет предполагать важную роль системы глутамата в регуляции пищевого поведения и, возможно, в патогенезе ВЕD, что дает основания для поиска фарма-копрепаратов, действующих на NMDA-рецепторы, в ка-честве лекарственных средств для терапии ВЕD [58].…”