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The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like eating, food-seeking behavior, and compulsive eating: role of the nucleus accumbens shell.

ABSTRACT: 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.

SUBMITTER: Smith KL

PROVIDER: S-EPMC4367459 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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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 Karen L KL Rao Rahul R RR Velázquez-Sánchez Clara C Valenza Marta M Giuliano Chiara C Everitt Barry J BJ Sabino Valentina V Cottone Pietro P

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150313 5

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 disorde ...[more]

PMID: 25381776

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Project description:Intravenous N-methyl-d-aspartate (NMDA) antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder.Adult outpatients with major depressive disorder and partial response or nonresponse to their current antidepressant (as indicated by a 17-item Hamilton Depression Rating Scale score of ? 16 at baseline) were randomized (from July 2006-December 2011) to add memantine (flexible dose 5-20 mg/d, with all memantine group participants reaching the dose of 20 mg/d) (n = 15) or placebo (n = 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated-measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects.84% of participants completed the trial, including 93% of participants receiving memantine. Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (? = 0.133, favoring placebo, P = .74) or at study completion (week 8 mean [SD] MADRS score change = -7.13 [6.61] [memantine]; -7.25 [11.14] [placebo]; P = .97). A minimal to small effect size (comparing change to baseline variability) favoring placebo was observed (Cohen d = 0.19). Similarly, no substantial effect sizes favoring memantine nor statistically significant between-group differences were observed on secondary efficacy outcomes.This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment for major depressive disorder.ClinicalTrials.gov identifier: NCT00344682.

Project description:Depressive symptoms and binge eating are both prevalent in weight management populations and may be associated with reduced benefit from behavioral weight loss, including higher attrition, more perceived barriers, lower weight loss, and increased weight regain. These two potential risk factors for poor behavioral weight loss outcomes may also be associated with each other as depressive symptoms may trigger binge eating, and binge eating-related distress could increase depressive symptoms. The depressive symptom-binge eating link has not been well studied in weight management samples, and psychological processes involved in this relationship have not yet been elucidated. Psychological flexibility, an individual's ability to be connected with and conscious of the present moment and to engage in values-consistent behavior even in the presence of difficult internal experiences, may be one psychological process that changes the depressive symptom-binge eating relationship. High psychological flexibility may be a protective factor in the association of depressive symptoms with binge eating. This study examined the relationship between depressive symptom and binge eating and a potential interactive role of psychological flexibility. Participants (N = 468, 76% female) completed self-report questionnaires of binge eating, depressive symptoms, and psychological flexibility at baseline prior to initiating behavioral weight loss. Depressive symptoms were positively associated with binge eating (B = 1.00, p < 0.001). Psychological flexibility had an interactive role (B = -0.03, p = 0.005). Among participants with minimal to mild depressive symptoms, those with higher psychological flexibility had less severe binge eating. Findings suggest that psychological flexibility may be a protective factor in the association between depressive symptoms and binge eating in the majority of individuals initiating behavioral weight loss. Psychological flexibility is a psychological process to consider targeting for enhancing efficacy of weight loss treatment, especially among individuals with minimal to mild depressive symptoms and binge eating behavior.

Dataset Information

The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like eating, food-seeking behavior, and compulsive eating: role of the nucleus accumbens shell.

Publications

The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like eating, food-seeking behavior, and compulsive eating: role of the nucleus accumbens shell.

Similar Datasets

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