Palatable Food Intake Research Articles

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge\xa0eating disorder

Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg−1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

Exogenous Orexin-A Microinjected Into Central Nucleus of the Amygdala Modulates Feeding and Gastric Motility in Rats.

Orexin-A is a circulating neuropeptide and neurotransmitter that regulates food intake and gastric motility. The central nucleus of the amygdala (CeA), which regulates feeding behavior and gastric function, expresses the orexin-1 receptor. The aim of this study was to evaluate the effects of microinjection of exogenous orexin-A into the CeA, on food intake and gastric motility, and to explore the mechanisms of these effects. Normal chow and high fat food (HFF) intake were measured, gastric motility and gastric emptying were evaluated, extracellular single unit firing was recorded, and c-fos expression was determined. The results showed that microinjection of orexin-A into the CeA resulted in increased HFF intake but did not affect normal chow intake. This effect was blocked by an orexin-1 receptor antagonist-SB-334867 and was partially blocked by a dopamine D1 receptor antagonist-SCH-23390. Gastric motility and gastric emptying were enhanced by orexin-A, and the former effect was abolished by subdiaphragmatic vagotomy. The firing frequency of gastric distention-related neurons was regulated by orexin-A via the orexin-1 receptor. Furthermore, c-fos expression was increased in the ventral tegmental area (VTA) and the nucleus accumbens (NAc), the lateral hypothalamus (LHA), and the dorsal motor nucleus of the vagus (DMV) in response to microinjection of orexin-A into the CeA. These findings showed that orexin-A regulated palatable food intake and gastric motility via the CeA. The LHA, the VTA, and the NAc may participate in palatable food intake and the CeA-DMV-vagus-stomach pathway may be involved in regulating gastric motility through the regulation of neuronal activity in the CeA.

Glucagon-like peptide-1 receptors and sexual behaviors in male mice

The gut-brain peptide glucagon-like peptide-1 (GLP-1) reduces reward from palatable food and drugs of abuse. Recent rodent studies show that activation of GLP-1 receptors (GLP-1R) within the nucleus of the solitary tract (NTS) not only suppresses the motivation and intake of palatable food, but also reduces alcohol-related behaviors. As reward induced by addictive drugs and sexual behaviors involve similar neurocircuits, we hypothesized that activation of GLP-1R suppresses sexual behavior in sexually naïve male mice. We initially identified that systemic administration of the GLP-1R agonist, exendin-4 (Ex4), decreased the frequency and duration of mounting behaviors, but did not alter the preference for females or female bedding. Thereafter infusion of Ex4 into the NTS decreased various behaviors of the sexual interaction chain, namely social, mounting and self-grooming behaviors. In male mice tested in the sexual interaction test, NTS-Ex4 increased dopamine turnover and enhanced serotonin levels in the nucleus accumbens (NAc). In addition, these mice displayed higher corticosterone, but not testosterone, levels in plasma. Finally, GLP-1R antagonist, exendin-3 (9-39) amide (Ex9), infused into the NTS differentially altered the ability of systemic-Ex4 to suppress the various behaviors of the sexual interaction chain, indicating that GLP-1R within the NTS is one of many sub-regions contributing to the GLP-1 dependent sexual behavior link. In these mice NTS-Ex9 partly blocked the systemic-Ex4 enhancement of corticosterone levels. Collectively, these data highlight that activation of GLP-1R, specifically those in the NTS, reduces sexual interaction behaviors in sexually naïve male mice and further provide a link between NTS-GLP-1R activation and reward-related behaviors.

Role of Dopamine D2 Receptor in the Leptin Receptor‐expressing Neurons in Modulation of Compulsive‐like Eating Behavior

Leptin, a hormone secreted by adipose tissue, is known to modulate satiety, caloric intake and body weight. There are six alternative spliced isoforms of leptin receptors (LepRa‐f). LepRb is highly expressed in the hypothalamic arcuate nucleus (ARC) which is involved in the regulation of food intake and body weight. Leptin activates pro‐opiomelanocortin‐expressing (POMC) neurons and inhibits agouti‐related peptide (AgRP)‐expressing neurons in the ARC.A recent study shows that dopamine modulates neuronal activities of arcuate POMC neurons and AgRP neurons. Dopamine inhibits arcuate POMC neurons via dopamine D2 receptor but activates AgRP neurons through dopamine D1 receptor. Dopamine is a neurotransmitter that plays a key role in mood, motivation and satiety. Dysregulation of dopamine neurotransmission is involved in the drug addiction. Food addiction is a recently proposed concept and compulsive eating behavior is shown in food addiction as well as an obesity. Negative reinforcement in drug addiction is a concept that negative affect associated with drug withdrawal promotes drug taking to ‘self‐medicate’ or remove those negative states. In the present study, we generated mice lacking D2 receptor in cells expressing LepRb (D2R flox; LepRb‐Cre; D2R cKO). Mice were provided palatable food for more than two weeks to induce food‐addiction like phenotypes in mice. To examine the role of D2 receptor in the leptin receptor‐expressing neurons in modulation of compulsive‐like eating behavior, light‐dark conflict test (LD test) was performed during the palatable food withdrawal period. In addition, palatable food withdrawal‐mediated anxiety/depression‐like behavior were measured during marble burying test (MBT), elevated plus maze (EPM), open filed test (OFT), and forced swim test (FST). No significant changes were found in palatable food (PF) intake in the light box during LD test, suggesting that D2 receptor in cells expressing LepRb would not be involved in the regulation of compulsive eating behavior. Furthermore, there was no significant changes in anxiety/depression‐like behavior measured by MBT, EPM, OPT and FST during the PF withdrawal period.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1I1A1A01060007).

Binge-like palatable food intake in rats reduces preproglucagon in the nucleus tractus solitarius

Binge eating involves eating larger than normal quantities of food within a discrete period of time. The neurohormonal controls governing binge-like palatable food intake are not well understood. Glucagon-like peptide-1 (GLP-1), a hormone produced peripherally in the intestine and centrally in the nucleus tractus solitarius (NTS), reduces food intake. Given that the NTS plays a critical role in integrating peripheral and central signals relevant for food intake, as well as the role of GLP-1 in motivated feeding, we tested the hypothesis that expression of the GLP-1 precursor preproglucagon (PPG) would be reduced in the NTS of rats with a history of binge-like palatable food intake. Adult male rats received access to fat for 1 h shortly before lights off, either every day (Daily, D) or only 3d/week (Intermittent, INT). INT rats ate significantly more fat than did D rats in sessions where all rats had fat access. After ~8.5 weeks of diet maintenance, we measured plasma GLP-1 as well as NTS PPG and GLP-1 receptor expression. INT rats had significantly lower NTS PPG mRNA expression compared to D rats. However, plasma GLP-1 was significantly increased in the INT group versus D rats. No significant differences were observed in NTS GLP-1 receptor expression. We also measured plasma insulin levels, fasted blood glucose, and plasma corticosterone but no differences were detected between groups. These results support the hypothesis that binge-like eating reduces NTS GLP-1 expression, and furthermore, demonstrate divergent impacts of binge-like eating on peripheral (plasma) versus central GLP-1.

The orexinergic neural pathway from the lateral hypothalamus to the nucleus accumbens and its regulation of palatable food intake

ObjectiveTo explore the orexinergic pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) and its regulation on the palatable food intake. MethodsFluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining were used to observe the projection of orexinergic neurons from LHA to NAc. The orexin-A expression in LHA and c-Fos in NAc were studied after electrical stimulation of LHA. The firing rates of neurons were monitored by single-unit extracellular electric discharge recording and the palatable food intake were measured after orexin microinjection in NAc or electrical stimulation of LHA. Results(1) Fluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining showed some orexinergic neural projection from the LHA to the NAc shell. (2) Electrical stimulation of LHA significantly enhanced the expression of orexin-A in LHA and the expression of c-Fos in NAc (P < .05). (3) The results of single-unit extracellular discharge recording showed that the microinjection of orexin in NAc or electrical stimulation of LHA significantly increased the discharge activity of gastric distension responsive neurons in NAc, and the effect could be partly blocked by pretreatment of orexin-A receptor inhibitor SB334867 in NAc (P < .05). (4) Microinjection orexin-A in NAc or electrical stimulation of LHA significantly increased the palatable food intake in rats, and the effect also was partly inhibited by pretreatment of SB334867 in NAc (P < .05). ConclusionThere is an orexinergic pathway from LHA to NAc, which may have potential regulatory effects on food reward and obesity.

Early weaning leads to disruption of homeostatic and hedonic eating behaviors and modulates serotonin (5HT) and dopamine (DA) systems in male adult rats

Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5HT and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5HT and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5HT1B, 5HT2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5HT1B mRNA expression. In the brainstem, the expression of 5HT1B, SERT, 5HT2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5HT and DA systems.

P.203 Intranasal insulin decreases palatable food intake, increases satiety and enhances positive mood in women with obesity

P.203 Intranasal insulin decreases palatable food intake, increases satiety and enhances positive mood in women with obesity

Ovarian Hormones and Reward Processes in Palatable Food Intake and Binge Eating.

Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contribute to these relationships, but additional studies are needed to confirm and extend findings.

Dual exposure to stress in different stages of development affects eating behavior of male Wistar rats

Maternal separation stress is a model of early life stress performed by the separation between dam and pups in the first days of life. The consequences of this early stress have been demonstrated on various behaviors, including feeding behavior. The results, however, are still controversial and it seems that a second exposure to stress later in life exacerbates the adverse outcomes. The present study aimed to determine the effects of maternal separation as a model of stress in early life, with or without a later life stress experience on eating behavior. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The groups control (C) and separated (S) were composed. The assessment of food intake was performed between the ages of 60 and 150 days of life with a group that experienced only the early stress by maternal separation and with a second group that experienced the pre-weaning maternal separation stress and the food stress from 60 days of age. This food stress consisted of allowing visual and olfactory exposure of the animals to palatable food but did not allow the feeding. Maternal separation promoted higher palatable food and lower standard diet intake only after a double exposure to stress. Besides, the double exposure to stress promoted weight loss and an anxiety-like behavior. These outcomes were associated with a resistance to the anorectic effects of fluoxetine suggesting an alteration of the serotonergic system. Together, these findings indicate that maternal separation stress has long-lasting consequences on eating behavior, and that the dual exposure to stress seems more harmful to eating behavior outcomes. In addition, the results suggest that the serotonergic system is one candidate as the system mediating these alterations.

Reduced Medial Prefrontal Control of Palatable Food Consumption Is Associated With Binge Eating Proneness in Female Rats.

Binge eating is the core, maladaptive eating behavior that cuts across several major types of eating disorders. Binge eating is associated with a significant loss of control over palatable food (PF) intake, and deficits in behavioral control mechanisms, subserved by the prefrontal cortex (PFC), may underlie binge eating. Few studies, to date, have examined whether the PFC is directly involved in the expression of binge eating. As such, the present study investigated the functional role of the medial PFC (mPFC) in PF consumption, using an individual differences rat model of binge eating proneness. Here, we tested the hypothesis that binge eating proneness (i.e., high levels of PF consumption) is associated with reduced mPFC-mediated behavioral control over PF intake. In experiment 1, we quantified PF-induced Fos expression in both excitatory and inhibitory neurons within the mPFC in binge eating prone (BEP) and binge eating resistant (BER) female rats. In experiment 2, we pharmacologically inactivated the mPFC of BEP and BER female rats, just prior to PF exposure, and subsequently quantified PF intake and scores of feeding behavior. While most Fos-expressing neurons of the mPFC in both BEPs and BERs were of the excitatory phenotype, fewer excitatory neurons were engaged by PF in BEPs than in BERs. Moreover, pharmacological inactivation of the mPFC led to a significant increase in PF intake in both BEPs and BERs, but the rise in PF consumption was stronger in BEPs than in BERs. Thus, these data suggest that lower, PF-induced excitatory tone in the mPFC of BEP rats may lead to a weaker, mPFC-mediated behavioral “brake” over excessive PF intake.

An 8-Week Relaxation Program Consisting of Progressive Muscle Relaxation and Mindfulness Meditation to Reduce Stress and Attenuate Stress-Driven Eating.

Stress is often associated with the intake of energy-dense palatable foods. This trial examined the feasibility and preliminary efficacy of an 8-week worksite-based relaxation intervention to address psychological stress and unhealthy food intake. Thirty-six men and women were exposed to an acute stressor, while physiological and psychological responses were assessed, prior to being offered a test meal. Participants were then randomised to a relaxation intervention (RELAX; face-to-face classes and daily home practice of progressive muscle relaxation and mindfulness meditation), or a wait-list control (CON). All measures were repeated after the intervention. Intervention compliance was high (80%±19% face-to-face; 79%±18% home practice), and each session acutely reduced perceived stress (p<.001) and increased relaxation (p<.001). After 8 weeks, trait mindfulness was increased (p=.025), along with reduced tension (p=.013) and increased relaxation (p<.05) post-acute stressor in the intervention group. There was no effect of the intervention on palatable eating, cravings, or energy intake at a laboratory test meal, with small associated effect sizes (d=0.01-0.3). The program studied here is feasible and sessions transiently reduce perceived stress and improve mindfulness; however, the program may not influence the physiological response to an acute stressor or appetite and eating variables.

Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

Binge eating (BE) is a heritable trait associated with eating disorders and involves episodes of rapid, large amounts of food consumption. We previously identified cytoplasmic FMR1-interacting protein 2 (Cyfip2) as a genetic factor underlying compulsive-like BE in mice. CYFIP2 is a homolog of CYFIP1 which is one of four paternally-deleted genes in patients with Type I Prader-Willi Syndrome (PWS), a neurodevelopmental disorder whereby 70% of cases involve paternal 15q11-q13 deletion. PWS symptoms include hyperphagia, obesity (if untreated), cognitive deficits, and obsessive-compulsive behaviors. We tested whether Cyfip1 haploinsufficiency (+/−) would enhance compulsive-like behavior and palatable food (PF) intake in a parental origin- and sex-dependent manner on two Cyfip2 genetic backgrounds, including the BE-prone C57BL/6N (Cyfip2N/N) background and the BE-resistant C57BL/6J (Cyfip2J/J) background. Cyfip1+/− mice showed increased compulsive-like behavior on both backgrounds and increased PF intake on the Cyfip2N/N background. In contrast, maternal Cyfip1 haploinsufficiency on the BE-resistant Cyfip2J/J background induced a robust escalation in PF intake in wild-type Cyfip1J/J males while having no effect in Cyfip1J/- males. Notably, induction of behavioral phenotypes in wild-type males following maternal Fmr1+/− has previously been reported. In the hypothalamus, there was a paternally-enhanced reduction in CYFIP1 protein whereas in the nucleus accumbens, there was a maternally-enhanced reduction in CYFIP1 protein. Nochange in FMR1 protein (FMRP) was observed in Cyfip1+/− mice, regardless of parental origin. To summarize, Cyfip1 haploinsufficiency increased compulsive-like behavior and induced genetic background-dependent, sex-dependent, and parent-of-origin-dependent effects on PF consumption and CYFIP1 expression that could have relevance for neurodevelopmental and neuropsychiatric disorders.

Accumbal TRH is downstream of the effects of isolation stress on hedonic food intake in rats

ABSTRACT Emotional stress, through elevating corticosterone (CORT) levels may reduce feeding in rodents however when offered palatable food, stressed animals ingest more food compared to non-stressed controls. Nucleus accumbens (NAc) is part of the mesocorticolimbic system and participates in processing rewarding characteristics of food modulating palatable food intake, mainly when glucocorticoids are elevated. A possible mediator of CORT effects is accumbal thyrotropin-releasing hormone (TRH), which reduces chow intake in rats when administered into the NAc. We aimed to study the TRH role in hedonic feeding in stressed rats. For 14 days, animals with ad libitum access to chow or chow plus chocolate milk were either group-housed or singly-housed to induce stress. Rats with access to chocolate milk showed hyperphagia and decreased accumbal TRH mRNA levels, which were potentiated by stress. Results suggest that TRH downregulation was permissive of the increased palatable food intake. TRH injections into NAc of singly-housed animals with palatable food access reduced their food intake and increased serum CORT levels. The accumbal injections of a glucocorticoid receptor antagonist (mifepristone) in stressed rats with palatable food access, reduced only palatable food intake and increased accumbal TRH expression and serum CORT levels. This modulation of TRH mRNA when CORT signaling is modified suggests that accumbal TRH is downstream of glucocorticoids activity, which specifically increase palatable food intake. Our results strengthen the TRH involvement in regulating emotional aspects of hedonic feeding in stressed animals. Finding new therapies directed towards increasing TRHergic activity in NAc may be protective against overeating.

Food craving predicts the consumption of highly palatable food but not bland food.

The impact of obesity on physical and psychological health is well recognized in the literature with, among others, evidence of alterations in cognition. Indeed, obese populations are characterized by lower executive functions as well as an enhanced food craving. However, the relationship between executive functions and food craving remains unexplored. Moreover, these two variables have also been shown to predict food intake, but studies in the context of obesity are lacking. Thus, this study had two objectives: (1) determining if executive functions and food craving are linked, and (2) examining the predictors of highly palatable food intake and bland food intake. First, it was hypothesized that executive functions would be negatively associated with food craving. Second, it was expected that food craving would predict positively highly palatable food intake but not bland food intake. Third, it was predicted that executive functions would predict negatively highly palatable food intake and positively bland food intake. 48 participants (34 females) with BMIs ranging from 17.9 to 46.4 took part in two experimental sessions. First, executive functions were assessed using the delayed discounting task (impulsivity towards food and money) and the color-word interference test (CWIT; inhibition/flexibility). Second, a cue-induced food craving protocol, with images as well as real food, was administered followed by an ad libitum food intake protocol including both highly palatable and bland food. The inhibition/flexibility condition of the CWIT was significantly and negatively correlated with food craving following induction. Highly palatable food intake was significantly predicted by food craving following induction, but bland food intake was not. This study reveals an association between lower inhibition/flexibility and susceptibility to food craving induction that is of great importance in obesogenic environments. Moreover, this study confirmed the link between food craving and food intake, and showed for the first time a specific contribution of food craving to highly palatable food intake but not to bland food intake, highlighting its potential influence in obesity. This work leads to future research questions regarding the possible benefits of cognitive remediation interventions, as well as interventions aiming at reducing food craving, in weight loss programs. LEVEL OF EVIDENCE: Level IV, quasi-experimental study.

VIPergic neurons of the infralimbic and prelimbic cortices control palatable food intake through separate cognitive pathways.

The prefrontal cortex controls food reward seeking and ingestion, playing important roles in directing attention, regulating motivation towards reward pursuit, and the assignment of reward salience and value. The cell types that mediate these behavioral functions, however, are not well described. We report here that optogenetic activation of vasoactive peptide expressing (VIP) interneurons in both the infralimbic (IL) and prelimbic (PL) divisions of the medial prefrontal cortex in mice is sufficient to reduce acute, binge-like intake of high calorie palatable food in the absence of any effect on low calorie rodent chow intake in the sated animal. In addition, we discovered that the behavioral mechanisms associated with these changes in feeding differed between animals that underwent either IL or PL VIPergic stimulation. While IL VIP neurons showed the ability to reduce palatable food intake, this effect was dependent upon the novelty and relative value of the food source. In addition, IL VIP neuron activation significantly reduced novel object- and novel social investigative behavior. Activation of PL VIP neurons, however, produced a reduction in high calorie palatable food intake that was independent of food novelty. Neither IL nor PL VIP excitation changed motivation to obtain food reward. Our data show how neurochemically-defined populations of cortical interneurons can regulate specific aspects of food reward-driven behavior, resulting in a selective reduction in intake of highly valued food.

Taste manipulation during a food cue-reactivity task: Effects on cue-elicited food craving and subsequent food intake among individuals with overweight and obesity

Food cue-reactivity tasks are used to induce and evaluate food cravings. Extant research has implicated the role of tasting foods in heightening cue-elicited food craving. The present study was the first to evaluate a taste manipulation during a food cue-reactivity task to optimize cue-elicited craving and predict food intake. Participants with overweight/obesity (N = 35; M age = 33.46 years [SD = 13.27]; M BMI = 32.91 kg/m2 [SD = 5.34]) engaged in one laboratory session and were randomized to a ‘No Taste’ or ‘Taste’ condition. All participants reported baseline food craving and observed two types of high-calorie food cues during a cue-reactivity task: photographic and real foods. The Taste group tasted real food cues and the No Taste group did not. Cue-elicited craving was assessed after the presentation of each food cue. Calorie intake of palatable foods was subsequently measured during a bogus taste test. Results indicated that cue-elicited craving to high-calorie foods was greater for the No Taste relative to the Taste group and that calorie intake was greater for the Taste relative to the No Taste group; both effects were nonsignificant, but of medium-size. Cue-elicited craving was significantly greater following exposure to high-calorie real food cues compared to photographic food cues. Results provide initial evidence that presenting high-calorie real (vs. photographic) food cues and forgoing taste manipulation during a food cue-reactivity task may optimize cue-elicited craving, and that taste manipulation could increase subsequent food intake. Future research should be conducted to replicate findings in larger samples with greater power to detect significant effects.

Reduced sensitivity to devaluation for instrumental but not consummatory behaviors in binge eating prone rats

Binge eating is characterized by the consumption of a large amount of palatable food in a short period of time and is a core feature of many eating disorders. Patients with eating disorders are also known to display impairments in inhibitory control, cognition and decision-making, which may promote and maintain binge eating symptomology. In the current study, we examined whether rats that were subsequently characterized as displaying a higher propensity to binge eat would show pre-existing deficits in reinforcer devaluation—a paradigm used to examine decision-making following reductions in the value of a food reinforcer. Female rats were first trained to respond on two levers for the delivery of two food reinforcers (sucrose and maltodextrin solutions). At the test stage, rats were provided 1 h access to one of the two reinforcers to allow for devaluation via sensory specific satiety, immediately followed by an extinction test with both levers. Normal rats typically show reductions in responding on the lever associated with the devalued reinforcer (i.e., intact goal-directed responding). Subsequently, we used intermittent access to palatable food to identify high (BE prone [BEP]; n = 14), intermediate (BE neutral [BEN]; n = 48), and low (BE resistant [BER]; n = 13) phenotypes of binge eating. Prior reinforcer devaluation performance showed BEN and BER rats suppressed responding on the lever associated with the devalued reinforcer while BEP rats did not. This insensitivity to instrumental reinforcer devaluation in BEP rats did not reflect impaired sensory-specific satiety as during a food choice test, BEP rats showed a more robust alteration in food preferences following devaluation. Additionally, across all rats sensory specific satiety was correlated with subsequent intake of palatable food. Collectively, these findings suggest dissociable effects of devaluation procedures on instrumental actions and consummatory behaviors in BEP rats, and may indicate that pre-existing differences in goal-directed behavior and sensory-specific satiety contribute to the propensity to overeat palatable food.

Intrauterine Growth Restriction Modifies the Accumbal Dopaminergic Response to Palatable Food Intake

Intrauterine growth restriction (IUGR) associates with increased preference for palatable foods and altered insulin sensitivity. Insulin modulates the central dopaminergic response and changes behavioral responses to reward. We measured the release of dopamine in the accumbens during palatable food intake in IUGR rats both at baseline and in response to insulin. From pregnancy day 10 until birth, gestating Sprague–Dawley rats received either an ad libitum (Control), or a 50% food restricted (FR) diet. In adulthood, palatable food consumption and feeding behavior entropy was assessed using an electronic food intake monitor (BioDAQ®), and dopamine response to palatable food was measured by chronoamperometry recordings in the nucleus accumbens (NAcc). FR rats eat more palatable foods during the dark phase, and their eating pattern has a higher entropy compared to control rats. There was a delayed dopamine release in the FR group in response to palatable food and insulin administration reverted this delayed effect. Western blot showed a decrease in suppressor of cytokine signaling 3 protein (SOCS3) in the ventral tegmental area (VTA) and an increase in the ratio of phospho-tyrosine hydroxylase to tyrosine hydroxylase (pTH/TH) in the NAcc of FR rats. Administration of insulin also abolished this latter effect in FR rats. FR rats showed metabolic alterations and a delay in the dopaminergic response to palatable foods. This could explain the increased palatable food intake and behavioral entropy found in FR rats. IUGR may lead to binge eating, obesity and its metabolic consequences by modifying the central dopaminergic response to sweet food.

Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans

Pleasant taste and nutritional value guide food selection behavior. Here, orosensory features of food may be secondary to its nutritional value in underlying reinforcement, but it is unclear how the brain encodes the reward value of food. Orosensory and peripheral physiological signals may act together on dopaminergic circuits to drive food intake. We combined fMRI and a novel [11C]raclopride PET method to assess systems-level activation and dopamine release in response to palatable food intake in humans. We identified immediate orosensory and delayed post-ingestive dopamine release. Both responses recruit segregated brain regions: specialized integrative pathways and higher cognitive centers. Furthermore, we identified brain areas where dopamine release reflected the subjective desire to eat. Immediate dopamine release in these wanting-related regions was inversely correlated with, and presumably inhibited, post-ingestive release in the dorsal striatum. Our results highlight the role of brain and periphery in interacting to reinforce food intake in humans.