Binge-like Eating Research Articles

Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating

Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24 h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1 h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder.

Increased Mesohippocampal Dopaminergic Activity and Improved Depression-Like Behaviors in Maternally Separated Rats Following Repeated Fasting/Refeeding Cycles

We have previously reported that rats that experienced 3 h of daily maternal separation during the first 2 weeks of birth (MS) showed binge-like eating behaviors with increased activity of the hypothalamic-pituitary-adrenal axis when they were subjected to fasting/refeeding cycles repeatedly. In this study, we have examined the psychoemotional behaviors of MS rats on the fasting/refeeding cycles, together with their brain dopamine levels. Fasting/refeeding cycles normalized the ambulatory activity of MS rats, which was decreased by MS experience. Depression-like behaviors, but not anxiety, by MS experience were improved after fasting/refeeding cycles. Fasting/refeeding cycles did not significantly affect the behavioral scores of nonhandled (NH) control rats. Fasting/refeeding cycles increased dopamine levels not only in the hippocampus but also in the midbrain dopaminergic neurons in MS rats, but not in NH controls. Results demonstrate that fasting/refeeding cycles increase the mesohippocampal dopaminergic activity and improve depression-like behaviors in rats that experienced MS. Together with our previous paper, it is suggested that increased dopamine neurotransmission in the hippocampus may be implicated in the underlying mechanisms by which the fasting/refeeding cycles induce binge-like eating and improve depression-like behaviors in MS rats.

Meal schedule influences food restriction-induced locomotor sensitization to methamphetamine

Traditional protocols for inducing sensitization to psychostimulants use an intermittent or "binge"-like drug administration, and binge eating behavior is comorbid with drug abuse in humans. Food restriction increases the reinforcing properties and self-administration of many drugs of abuse. The present study tested the hypotheses that (1) food restriction induces sensitization to the locomotor stimulation observed in response to methamphetamine and (2) a binge-like feeding schedule during food restriction produces increased sensitization compared to equally restricted mice fed in three daily meals. Male DBA/2J mice were fed ad libitum or were food restricted to either an 8% or 16% loss of body weight. Additionally, the food-restricted mice were divided into two groups that were fed in either one meal (binge) or three equal-sized meals (meal). After the reduced body weight was stable, mice were tested for locomotor activity following saline and methamphetamine (1 mg/kg) injections. Both 16% body weight loss groups exhibited sensitization to methamphetamine. Opposite to our hypothesis, the 8% meal but not the 8% binge food-restricted group demonstrated locomotor sensitization. Serum corticosterone levels were significantly higher in the meal-fed groups when compared to the binge- and ad libitum-fed groups. These results support a role for feeding schedule and plasma corticosterone levels in food restriction-induced enhancement of the effects of methamphetamine.

A Model of Binge‐Like Eating Behavior in Mice That Does Not Require Food Deprivation or Stress

Binge eating disorder (BED) is characterized by excessive food intake during a short period of time and is often associated with obesity. Mouse models of binge-like eating behavior are lacking making it difficult to employ genetic models in the identification of mechanisms regulating excessive eating. We report a rapid and simple model to induce binge-like eating behavior in mice that does not require food deprivation or exogenous stressors. Weekly 24 h access to a nutritionally complete high energy diet (HED), along with continuous access to standard chow, resulted in a significant increase in HED intake following its presentation compared to mice that had continuous access to both diets. Mice exhibiting binge-like eating consumed one-third of their normal total daily caloric intake within 2.5 h of HED presentation. Moreover, total 24-h caloric intakes were increased by 50% in mice exhibiting binge-like eating. Following repeated cycles, binge-like eating of the HED was maintained over several weeks with no evidence of habituation or significant alterations in body weight and adiposity. Pharmacological evaluation of binge-like eating behavior was performed using clinically employed compounds. Interestingly, binge-like eating was dose-dependently decreased by fluoxetine, but not baclofen or topiramate. These data support clinical validation of this mouse model of binge-like eating behavior, as fluoxetine has been shown to reduce binge frequency in human subjects with BED. The availability of transgenic and knockout mice will allow for the determination of genes that are involved in the initiation and maintenance of binge-like eating behavior.

Binge‐like eating in mice

Given the lack of reliable murine model of binge-like eating, we tried to induce this pathological behavior in mice. We used an experimental protocol mimicking the etiological factors involved in the development of binge eating in humans, that is, food restriction, refeeding (R-R) in presence of high palatable food, and stress (S). Mice subjected to at least three cycles of R-R plus S (forced swimming stress), showed a binge-like behavior evident as early as 4 h, persisting 24 h after stress application and not associated to depressive-like behavior. However, after the third R-R/S cycle, food intakes of mice returned to normal levels. (i) at least three cycles of R-R plus S are required to promote abnormal eating in mice, (ii) this is not associated to depressive-like behaviors, and (iii) the enhanced pathological behavior showed a transient nature not persisting after the third R-R/S cycle.

Differences in binge-like eating patterns of a palatable dessert and body weight gain in young and old female rats.

It has been suggested that uncertain or variable availability of food leads to patterns of restriction and overconsumption, which is a component of binge-like eating in humans. This behavior has been modeled in female rats given either daily (low restriction, LR) or every-other-day (high restriction, HR) access to shortening (Dimitriou et al., 2000); only HR rats consumed significantly more total calories on days with shortening access. However, this protocol did not result in a change in body weight. To address this problem, we modified the protocol to use a sugar-fat whip dessert (SFW; 2 parts vegetable shortening to 1 part sugar, 7.35 kcal/g) that has promoted significant weight gain in our previous free access protocols. Both young (90 days of age) and retired breeder female (>1 year) Sprague Dawley rats were provided with either LR or HR 2 h nocturnal access to SFW conjunction with ad libitum access to moist chow (MC; 1 part standard Purina 5001 powdered chow to 1 part tap water, 1.67 kcal/g) for 6 weeks. Young HR rats exhibited binge-like eating and a trend towards increased body weight, but young LR rats did not. This pattern was not seen in old HR rats, which consumed amounts similar to old LR rats, but did not gain as much weight. This suggests that age and perhaps levels of sex hormones play an important role in the mediation of binge-like eating and weight gain due to overconsumption.

Effect of level of dysfunction of the melanocortin-4 receptor (MC4R) on overconsumption and binge-like eating of a palatable dessert in mice.

Dysfunction of the melanocortin-4 receptor (MC4R) leads to hyperphagia and overweight and has been correlated with obesity and binge-eating in humans. We examined in mice the effect of MC4R dysfunction on development of overconsumption and body weight gain. Wild type (WT) mice, homozygous MC4R knockout (MC4RKO), and carrier (MC4RHET) mice were provided with ad libitum access to moist chow (1:1 powdered Purina 5001 to tap water, 1.67 kcal/g) and daily 8 h access to sugar fat whip (SFW; 2:1 vegetable shortening to sugar, 7.35 kcal/g). MC4RKO mice increased their caloric intake and gained weight. This is indicative of a role of MC4R in maintaining caloric balance and adjusting to the consumption of palatable foods. MC4RHET mice ate similarly to WT mice, which, unlike rats, maintained caloric balance. This suggests that studies of MC4RKO mice may be a more valid model of human overconsumption. We also examined the effect of MC4R dysfunction on binge-like eating patterns in a protocol similar to Corwin's group (Dimitriou et al., 2000). We provided female mice either daily (low restriction, LR) or every-other-day (high restriction, HR) 2 h access to SFW. HR mice of all genotypes showed evidence of binge-like eating, but only MC4RKO mice gained weight. This suggests that a lack of MC4R functioning may not be necessary for the development of binge-like eating, but may be associated with the obesity related to it.

A history of binge-type feeding leads to alterations in forebrain dopamine and hindbrain c-Fos immunoreactivity in rats.

To model the restriction and re-feeding exhibited by bulimics, two groups of adult male Sprague Dawley rats were exposed to repeated cycles of 3 days of no restriction, caloric restriction (33% of the daily kcal of “no restriction” days), and re-feeding 2 h into the dark period. Conditions were similar between the two groups, except that on the re-feeding days the BINGE group received chow and a 2 h access to sweetened fat (90% Crisco and 10% sucrose blend), whereas the CONTROL group received only chow. In the first experiment in which the restriction/re-feeding cycles were repeated for 3 weeks, two subgroups from each group were sacrificed immediately BEFORE or AFTER the scheduled re-feeding. Regional forebrain tissue homengates were subjected to HPLC/EC for monoamine detection. The BEFORE-BINGE group ( n =2) had lower hypothalamic dopamine levels than the BEFORE-CONTROLS ( n =3, p <0.05), whereas the AFTER- BINGE group ( n =3) had lower prefrontal cortical dopamine levels than the AFTER-CONTROLS ( n =3, p <0.05). In another experiment in which the restriction/re-feeding cycles were repeated for 5 weeks, both groups were sacrificed 90 min following the re-feeding of a “clamped” amount of sweetened fat and chow. The BINGE group ( n =6) had more c-Fos immunopositive cells in the caudal and intermediate regions of the nucleus of the solitary tract than the CONTROLS ( n =6; p <0.05, for both regions). These results suggest that a history of calorie restriction followed by access to a sweet/fatty food leads to forebrain and hindbrain alterations that may be involved in perpetuating binge-like eating. Supported by DK070707 and MH015330.

Opioid-Dependent Anticipatory Negative Contrast and Binge-Like Eating in Rats with Limited Access to Highly Preferred Food

Binge eating and an increased role for palatability in determining food intake are abnormal adaptations in feeding behavior linked to eating disorders and body weight dysregulation. The present study tested the hypothesis that rats with limited access to highly preferred food would develop analogous opioid-dependent learned adaptations in feeding behavior, with associated changes in metabolism and anxiety-like behavior. For this purpose, adolescent female Wistar rats were daily food deprived (2 h) and then offered 10-min access to a feeder containing chow followed sequentially by 10-min access to a different feeder containing either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable, sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge-like hyperphagia of preferred diet from the second feeder and anticipatory chow hypophagia from the first feeder with a time course suggesting associative learning. The feeding adaptations were dissociable in onset, across individuals, and in their dose-response to the opioid-receptor antagonist nalmefene, suggesting that they represent distinct palatability-motivated processes. Chow/preferred-fed rats showed increased anxiety-like behavior in relation to their propensity to binge as well as increased feed efficiency, body weight, and visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short-term control of food intake in rats with restricted access to highly preferred foods comes to rely more on hedonic, rather than nutritional, properties of food, through associative learning mechanisms. Such rats show changes in ingestive, metabolic, endocrine, and anxiety-related measures, which resemble features of binge eating disorders or obesity.

Diverging Sex-morbidity Trends in Cancer of the Mouth

<h3>Abstract</h3> Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When tested with an intermittent access to HFD where first 2.5-h HFD eating (binge-like) and 24-h HFD feeding were measured, KO mice exhibited more binge-like, but less 24-h HFD feeding. Interestingly, leptin inhibited 24-h HFD feeding in controls but not in KO mice. Thus, VMAT2-mediated neurotransmission from midbrain LepR neurons contributes to both binge-like eating and HFD feeding regulation.