A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine

Foltin, Richard W.; Danysz, Wojciech; Bisaga, Adam

doi:10.1007/s00213-008-1178-8

Cited by 12 publications

(23 citation statements)

References 52 publications

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“…Results of the present study, as well as previous studies using animal models (Bisaga et al 2008; Foltin et al 2008), suggest that memantine may have a uniquely attractive profile of clinical effectiveness. Initial uncontrolled clinical observations confirm the safety and potential effectiveness of memantine in reducing binge-eating with less effect on weight (Brennan et al 2008; Hermanussen and Tresguerres 2005).…”

Section: Discussionsupporting

confidence: 83%

“…We have previously shown in baboons, that single doses of memantine and MTEP produce decrease in the consumption of highly palatable food (candy) comparable to effects of dexfenfluramine, another prototypic binge-eating reducing medication (Bisaga et al 2008; Foltin et al 2008). The second goal of the present study was therefore to evaluate the effects of the NMDA receptor antagonist memantine and the mGluR5 antagonist MTEP and to compare those effects to the effects of sibutramine in the limited-access animal model of binge-eating of highly palatable food (lard) and on the consumption of chow available at all times.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2010

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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.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 98%

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

et al. 2010

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“…Notably, a large body of evidence shows that memantine reduces the reinforcing and rewarding effects of drugs of abuse (Hart et al, 2002;Hyytia et al, 1999;Popik et al, 2003;Sabino et al, 2013). Interestingly, a few studies have suggested the ability of memantine also to reduce excessive intake of palatable food Foltin et al, 2008;Popik et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Smith

Rao

Velázquez-Sánchez

et al. 2014

Neuropsychopharmacol

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Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic N-methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive 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 the 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 the 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.

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“…Although the baboons were not food deprived, other than during the dark cycle, the procedure limited the variability in the pattern of food intake. Limiting the rate of food intake by forcing breaks between eating the 20 candies has been shown to provide an eating baseline that was sensitive to the hypothesized effects of drugs on satiation [27]. …”

Section: Introductionmentioning

confidence: 99%

Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons

Foltin

2011

Physiology & Behavior

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We examined the effects of periodic access to a palatable, high sugar content food (candy) in 8 male baboons on the anorectic response to d-amphetamine, which increases dopamine, and dexfenfluramine, which increases serotonin. During candy access, up to 200 candies containing 75% of energy as sugar were available during the morning on Mondays, Wednesdays and Fridays; food pellets (19% of energy as sugar) were available in the afternoon and throughout the remaining days of the week. During candy access, baboons consumed a mean of 177 pieces of candy containing 696 kcal (2.91 MJ) in the morning compared to 44 food pellets and 150 kcal (0.63 MJ) in the morning on non-candy days. Food pellet intake was lower during candy access. Complete dose-response functions for the effects of the drugs on food pellet intake on days that candy was not available were determined before, during, and after the period of access to candy. Dexfenfluramine and amphetamine produced dose-dependent decreases in food pellet intake and increases in latency to eat food pellets before, during, and after candy access. During access to candy, the dose-response function for dexfenfluramine was shifted to the right indicating the development of tolerance, while that for amphetamine was shifted to the left indicating sensitization. Only the dose-response function for dexfenfluramine returned to baseline after candy access suggesting that the difference was specific to concurrent palatable food consumption. We hypothesize that tolerance to the effects of dexfenfluramine reflects a decrease in the satiating effect of serotonin release due to repeatedly eating large amounts of palatable food.

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A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine

Cited by 12 publications

References 52 publications

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

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

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

Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons

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