Behavioral responses to natural rewards in developing male and female rats.

Reward deficits are a hallmark feature of multiple psychiatric disorders and often recapitulated in rodent models useful for the study of psychiatric disorders, including those employing early life stress. Moreover, rodent studies have shown sex differences during adulthood in response to natural and drug rewards under normative conditions and in stress-based rodent models. Yet, little is known about the development of reward-related responses under normative conditions, including how these may differ in rats of both sexes during early development. Comparing reward-related behavioral responses between developing male and female rats may be useful for understanding how these processes may be affected in rodent models relevant to psychiatric disorders. To this end, we tested behavioral responses to natural rewards in male and female rats using sucrose consumption, sweet palatable food intake and social play tests at two timepoints (peripuberty, adolescence). Our results suggest comparable responses to consummatory and social rewards in male and female rats during peripuberty and adolescence as no sex differences were found for sucrose preference, chocolate candy intake or a subset of play behaviors (dorsal contacts, pins). These findings suggest that sex differences in response to these natural rewards emerge and may be more robust during adulthood.

The potential effect of α7 nicotinic receptors modulation on palatable food-induced dependence-like behaviors.

Background: The recent global increase in obesity rates, coupled with excessive palatable food (PF) consumption, has become a serious societal concern. Literature indicates that rewarding PF, especially upon cessation, can lead to overeating, binge eating, and compulsive eating, potentially resulting in obesity. Challenges in dietary paradigms, alongside limitations in approved treatments for eating disorders and anti-obesity medications, underscore the need to explore novel targets. In this context, α7nAChR (alpha-7 nicotinic acetylcholine receptor) may serve as a promising therapeutic target in combating food dependence and obesity. The present study aims to assess the role of α7nAChR in palatable food-induced dependence-like behaviors. Method: The study involved male C57BL/6J mice exposed to three different feeding paradigms over 6 weeks to induce obesity and food addiction. On day 43, palatable food was replaced with standard chow, and the mice received treatments (vehicle, PNU-282987 [α7nAChR agonist], or methyllycaconitine citrate [MLA; α7nAChR antagonist]). Addiction-like behaviors, including craving for palatable food, motivation-effort interaction tests, and compulsive eating-like behavior, were measured during abstinence with and without treatment. Results: The present study shows that chronic intermittent and continuous exposure to palatable food induces craving, motivation, and effort interaction behaviors as well as compulsive eating-like behaviors in palatable food-abstinent mice. Administration of the α7nAChR agonist, PNU-282987, significantly attenuated the craving behavior only in mice continuously fed palatable food (reduced calorie intake from 63.19 % to 48.21 %; p = 0.0053). Also, PNU-282987 suppressed the effort behaviors in either intermittently or continuously fed mice (significant reduction in the Δ number of active events per minute; p-values = 0.038 and 0.0098, respectively). However, it attenuated the compulsive-like eating behavior exclusively in the continuously fed group (p = 0.0433). Active and total interaction efforts were reversed by the MLA. These findings indicate the involvement of α7nAChR in dependence-like behaviors toward palatable food in mice. Conclusion: Our findings demonstrate that dependence-like behaviors toward palatable food can emerge after prolonged exposure. Mice fed on palatable food continuously exhibited more dependence-like behaviors toward palatable food, and activation of α7nAChR signaling attenuated the vulnerability to develop such behaviors.

Corticostriatal dynamics underlying components of binge-like consumption of palatable food in mice.

Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. Despite the substantial negative impact of BE on psychological and physiological health, its underlying neural mechanisms are largely unknown. Other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. However, to date, no work has investigated the in vivo neural dynamics underlying corticostriatal activity during BE episodes. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions - the infralimbic cortex (IL) and dorsolateral striatum (DLS)- in a robust pre-clinical model for BE. Female C57BL6/J mice (N = 32) were randomized to receive: 1) intermittent (daily, 2-h) binge-like access to palatable food (sweetened condensed milk) (BE), or 2) continuous, non-intermittent (24-h) access to palatable food (control). In vivo calcium imaging was performed via fiber photometry at baseline and after chronic (4 weeks) engagement in the model for BE. Specific consummatory behaviors (feeding bout onset/offset) during recordings were captured using lickometers which generated TTL outputs for precise alignment of behavior to neural data. IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity at feeding onset and offset at the chronic timepoint when compared to activity at the baseline timepoint. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset at the chronic timepoint compared to control mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.

Hyper-palatable food consumption during binge-eating episodes: A comparison of intake during binge eating and restricting.

OBJECTIVE: The study aim was to elucidate the degree to which hyper-palatable foods (HPF) are consumed during binge episodes compared to restricting episodes, and to test the association between HPF intake during each episode and respective episode frequency. METHOD: This study was a secondary analysis of data from a larger study on eating disorders. The present sample included adults (N = 147, 83% women) diagnosed with sub-threshold (41%) or full-threshold (59%) bulimia nervosa (BN). Foods consumed during binge and restricting episodes were assessed using the Eating Pathology Symptoms Inventory-Clinician Rated Version. A standardized definition of HPF developed previously was applied to foods consumed during binge and restricting episodes. A Wilcoxon matched-pairs signed-rank test was used to test the difference between total caloric intake from HPF (KcalHPF) and percentage of caloric intake from HPF (PercHPF) during binge episodes relative to restricting episodes. Four linear regression models tested HPF intake (KcalHPF and PercHPF) during both episode types (binge and restricting) as predictors of respective episode frequency. RESULTS: There was a significant difference between median KcalHPF (1846.6 vs. 279.6; Z = -13.38, p < .001) and PercHPF during binge compared to restricting episodes (95% vs. 61%; Z = -7.35, p < .001). Regression analyses demonstrated that KcalHPF during binge episodes was significantly associated with binge episode frequency (B = 0.002; p < .001), but not PercHPF (p = .287). DISCUSSION: Results suggest that HPF may be primarily consumed during binge episodes among individuals with BN, and may be associated with greater binge-eating frequency. PUBLIC SIGNIFICANCE: Findings from the current study support an underlying assumption of theoretical models of binge eating, suggesting that highly rewarding, hyper-palatable foods (HPF), may constitute the vast majority of energy intake during binge-eating episodes. Additionally, a substantial amount of energy intake from HPF may occur during restricting episodes among people with bulimia nervosa. Greater HPF intake during binge eating may also be associated with binge-eating severity.

Serum metabolic signature of binge-like palatable food consumption in female rats by nuclear magnetic resonance spectroscopy.

Maladaptive eating behavior is a growing public health problem and compulsively eating excessive food in a short time, or binge eating, is a key symptom of many eating disorders. In order to investigate the binge-like eating behavior in female rats, induced by intermittent food restrictions/refeeding and frustration stress, we analyzed for the first time the metabolic profile obtained from serum of rats, through nuclear magnetic resonance (NMR) spectroscopy. In this experimental protocol, rats were exposed to chow food restricting/refeeding and frustration stress manipulation. This stress procedure consists of 15 min exposure to the odor and sight of a familiar chocolate paste, without access to it, just before offering the palatable food. In this model, a "binge-eating episode" was considered the significantly higher palatable food consumption within 2 h in restricted and stressed rats (R + S) than in the other three experimental groups: rats with no food restriction and no stress (NR + NS), only stressed rats (NR + S) or only restricted rats (R + NS). Serum samples from these four different rat groups were collected. The statistical analysis of the 1 H NMR spectral profiles of the four sets of samples pointed to O- and N-acetyl glycoproteins as the main biomarkers for the discrimination of restriction effects. Other metabolites, such as threonine, glycine, glutamine, acetate, pyruvate and lactate, showed trends that may be useful to understand metabolic pathways involved in eating disorders. This study suggested that NMR-based metabolomics is a suitable approach to detect biomarkers related to binge-eating behavior.

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

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.

Fat rather than sugar diet leads to binge-type eating, anticipation, effort behavior and activation of the corticolimbic system.

Objectives: One factor contributing to the development of obesity is overeating palatable food. The palatability of food is driven by specific energy yielding combinations and flavor profiles that may contribute to its overconsumption. In rodents, restricted access to palatable food (PF) is a strong stimulus to trigger binge-type eating behavior (BTE), food anticipatory activity (FAA), effort behaviors and withdrawal symptoms. This is accompanied by plastic changes in corticolimbic areas associated with motivation and reward responses. Palatable food contains mainly a mixture of fat and sugar, thus, the contribution of each macronutrient for the behavioral and neuronal changes is unclear.Methods: In this study, Wistar rats were exposed to restricted access to 50% fat rich diet (FRD) or 50% sugar rich diet (SRD) in order to compare the intensity of BTE, FAA, effort behaviors and withdrawal responses.Results: In corticolimbic areas, c-Fos activation and ΔFosB accumulation were evaluated. After an acute exposition, rats ate more SRD than FRD, but FDR stimulated higher c-Fos. After chronic administration, the FDR group exhibited higher levels of BTE and FAA; this was associated with higher c-Fos and accumulation of ΔFosB in the corticolimbic system. Similar effects in the FRD group were observed after one week of withdrawal.Discussion: Present data indicate that the fat rich diet is a stronger stimulus than the sugar rich diet for the development of wanting behavior for reward and the underlying plastic changes in the corticolimbic system. The differential effects may be due to the differing caloric density of the diets.

Multi-method assessment of palatable food exposure in women with and without eating disorders.

OBJECTIVE: Eating disorders (EDs) are characterized by dysregulated responses to palatable food. Using a multi-method approach, this study examined responses to palatable food exposure and subsequent ad libitum eating in women with binge-eating disorder (BED: n = 64), anorexia nervosa (AN: n = 16), and bulimia nervosa (BN: n = 35) and 26 healthy controls (HCs). METHOD: Participants were exposed to palatable food followed by an ad libitum eating opportunity. Affective and psychophysiological responses were measured before and during the task. RESULTS: Participants with EDs reported greater negative affect, particularly fear, following the food cue exposure, whereas HCs reported no change. BN and BED groups reported greater urge to binge after the food cue exposure, whereas AN and HC groups reported no change. Respiratory sinus arrhythmia levels, skin conductance and tonic skin conductance levels increased during food exposure for all groups. Across baseline and during the food exposure, the BED group had lower respiratory sinus arrhythmia levels relative to the BN and HC groups. The BED group consumed significantly more palatable food than the AN group. CONCLUSIONS: 'Palatable' food stimuli elicited more negative affect, particularly fear, in individuals with EDs; and this, rather than psychophysiological responses, distinguishes individuals with EDs from those without.

Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA.

In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by "rewiring" mesolimbic dopamine neurons.

Subchronic air pollution exposure increases highly palatable food intake, modulates caloric efficiency and induces lipoperoxidation.

The investigation of the relationship between air pollution and obesity has captured the interest of researchers. However, the mechanism regarding the association between air pollution exposure and metabolic diseases and obesity still remains unclear. We aimed to investigate the effects of subchronic ROFA exposure on consumption and preference for highly palatable food and its interference on biochemical, lipid and oxidative stress parameters in rats. Male Wistar rats were divided in groups: control, ROFA, chocolate and ROFA + chocolate. Rats were exposed to ROFA during 18 weeks and to palatable food in the last 30 days. Food consumption, caloric intake and caloric efficiency, body mass gain, abdominal fat deposition, glucose and lipid profile were measured. Thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activity were assessed in lungs, heart, pancreas and hypothalamus. Chocolate intake was higher in the first and second weeks in rats exposed to ROFA while the standard chow intake was smaller in second and third weeks. The amount of kilocalories derived from chocolate was higher in the animals exposed to ROFA in all weeks. The caloric intake and body mass gain were not different among groups. Triglycerides, total cholesterol and HDL were higher in chocolate exposed rats. The TBARS was higher in lung and heart in ROFA group and in hypothalamus in ROFA + chocolate group. There were no significant differences in glucose, LDL and antioxidant enzymes. These findings indicate that subcronic air pollution exposure can modulate metabolic effects of subacute exposure to chocolate in adulthood.

Fetal growth interacts with multilocus genetic score reflecting dopamine signaling capacity to predict spontaneous sugar intake in children.

BACKGROUND: We have shown that intrauterine growth restriction (IUGR) leads to increased preference for palatable foods at different ages in both humans and rodents. In IUGR rodents, altered striatal dopamine signaling associates with a preference for palatable foods. OBJECTIVES: Our aim was to investigate if a multilocus genetic score reflecting dopamine-signaling capacity is differently associated with spontaneous palatable food intake in children according to the fetal growth status. METHODS: 192 four-year old children from a community sample from Montreal and Hamilton, Canada, were classified according to birth weight and administered a snack test meal containing regular as well as palatable foods. Intrauterine growth restriction was based on the birth weight ratio below 0.85; children were genotyped for polymorphisms associated with dopamine (DA) signaling, with the hypofunctional variants (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10-repeat, Met/Met-COMT) receiving the lowest scores, and a composite score was calculated reflecting the total number of the five genotypes. Macronutrient intake during the Snack Test was the outcome. RESULTS: Adjusting for z-score BMI at 48 months and sex, there was a significant interaction of the genetic profile and fetal growth on sugar intake [߈ = -4.56, p = 0.04], showing a positive association between the genetic score and sugar intake in IUGR children, and no association in non-IUGR children. No significant interactions were seen in other macronutrients. CONCLUSIONS: Variations in a genetic score reflecting DA signaling are associated with differences in sugar intake only in IUGR children, suggesting that DA function is involved in this behavioral feature in these children. This may have important implications for obesity prevention in this population.

The duration of intermittent access to preferred sucrose-rich food affects binge-like intake, fat accumulation, and fasting glucose in male rats.

Many people restrict their palatable food intake. In animal models, time-limiting access to palatable foods increases their intake while decreasing intake of less preferred alternatives; negative emotional withdrawal-like behavior is sometimes reported. In drug addiction models, intermittent extended access drives greater changes in use than brief access. When it comes to palatable food, the impact of briefer vs. longer access durations within intermittent access conditions remains unclear. Here, we provided male rats with chow or with weekday access to a preferred, sucrose-rich diet (PREF) (2, 4, or 8 h daily) with chow otherwise available. Despite normal energy intake, all restricted access conditions increased weight gain by 6 weeks and shifted diet acceptance within 1 week. They increased daily and 2-h intake of PREF with individual vulnerability and decreased chow intake. Rats with the briefest access had the greatest binge-like (2-h) intake, did not lose weight on weekends despite undereating chow, and were fattier by 12 weeks. Extended access rats (8 h) showed the greatest daily intake of preferred food and corresponding undereating of chow, slower weight gain when PREF was unavailable, and more variable daily energy intake from week to week. Increased fasting glucose was seen in 2-h and 8-h access rats. During acute withdrawal from PREF to chow diet, restricted access rats showed increased locomotor activity. Thus, intermittent access broadly promoted weight gain, fasting hyperglycemia and psychomotor arousal during early withdrawal. More restricted access promoted greater binge-like intake and fat accumulation, whereas longer access promoted evidence of greater food reward tolerance.

Changes in the incentive value of food after naltrexone treatment depend on a differential preference for a palatable food in male rats.

INTRODUCTION: Opioid antagonist treatments such as naltrexone (NTX) and naloxone reduce consummatory behavior of palatable food (PF) and other incentives. Meanwhile, a significant increase in alcohol consumption has been observed when it is offered immediately after ending NTX treatment, an effect apparently produced by increased opioidergic activity caused by up-regulation of opioid receptors. OBJECTIVE: On this basis we assessed changes in the consumption of PF after opioid antagonist treatment in rats with different preferences for that food. METHODS: The preference of male Wistar rats for a PF was classified as low, medium, or high in a baseline period, after which the animals in each preference level were sub-divided into control and experimental groups that received injections of either NTX (2 mg/kg twice per day/6 days) or a saline solution with a space of 8 hours between doses. At the end of pharmacological treatment (PT), subjects were re-exposed to the PF. RESULTS: Increased PF intake was found only in the low-preference group, but the increase was observed in both the experimental and control animals. Also, a decrease in chow intake during PT was observed in all preference groups, while recovery after treatment was noted only in the low-preference rats. DISCUSSION: The increased intake observed in the low-preference rats after treatment phase suggests that the hypothalamic-pituitary-adrenal axis activation during PT could have enhanced the rewarding characteristics of the sweet food and so facilitated and increased its consumption in the re-exposure period.

Palatable food consumption in children: interplay between (food) reward motivation and the home food environment.

To understand the importance of the home food environment on unhealthy food consumption in children high in reward sensitivity, this study tested the hypothesis that the home availability of unhealthy food moderates the effect of reward sensitivity on children's fast-food consumption frequency, exerted via food cue responsiveness. Children between 7.5 and 14 years (n = 174, 50.6% boys) reported on reward sensitivity and food cue responsiveness (by means of the subscale 'external eating'). Their height and weight were measured. Parents reported on their children's fast-food consumption frequency, food cue responsiveness (by means of the subscale 'food responsiveness'), and on the home availability of unhealthy foods. Two moderated mediation models were conducted, one with the parent- and one with the child-reported food cue responsiveness as mediator. Findings suggested that with a high home availability of unhealthy foods, (a) a higher fast-food consumption frequency was found in children high in reward sensitivity and (b) the relation between reward sensitivity and the fast-food consumption frequency was mediated by external eating. CONCLUSIONS: The findings point at the importance of the home food environment in children high in reward sensitivity. They suggest to limit the home availability of unhealthy foods. What is Known: • Reward sensitivity (RS) is positively associated with children's palatable food consumption • In adolescents, this effect is mediated by food cue responsiveness, which determines the strength of an individual's motivation to obtain food when perceiving food cues What is New: • Children high in RS may be more vulnerable to palatable food cues in their everyday food environment because of a higher food cue responsiveness • The home food environment may be an important determining factor of the palatable food consumption of these children.

The neurobiological and behavioral overlaps of nicotine and food addiction.

Both cigarette smoking and obesity are significant public health concerns and are associated with increased risk of early mortality. It is well established that the mesolimbic dopamine pathway is an important component of the reward system within the brain and is implicated in the development of addiction. Indeed, nicotine and highly palatable foods are capable of altering dopamine release within this system, engendering addictive like responses in susceptible individuals. Although additional research is warranted, findings from animal and human literature have elucidated many of neuroadaptions that occur from exposure to nicotine and highly palatable foods, leading to a greater understanding of the underlying mechanisms contributing to these aberrant behaviors. In this review we present the findings taken from preclinical and clinical literature of the known effects of exposure to nicotine and highly palatable foods on the reward related circuitry within the brain. Further, we compare the neurobiological and behavioral overlaps between nicotine, highly palatable foods and obesity. Lastly, we examine the stigma associated with smoking, obesity and food addiction, and the consequences stigma has on the overall health and wellbeing of an individual.

Effect of adapted interpersonal psychotherapy versus health education on mood and eating in the laboratory among adolescent girls with loss of control eating.

OBJECTIVE: Interpersonal psychotherapy (IPT) is aimed at improving negative affect that is purported to contribute to the development and maintenance of loss-of-control (LOC) eating. Although youth who report LOC over eating tend to consume more snack-foods than those without LOC, it is unknown if IPT impacts objective energy intake. METHODS: To test if IPT improves mood and eating in the laboratory, we examined a sample of 88 girls with LOC eating who were randomized to either IPT (n = 46) or a standard-of-care health education (HE) group program. At baseline, and 6-month (follow-up 1) and 1-year (follow-up 2) following the initiation of the groups, girls consumed lunch from a multi-item meal with an instruction designed to model a LOC episode. Girls also reported mood state immediately before each meal. RESULTS: Girls in IPT experienced no significant changes in pre-meal state depressive affect, while girls in HE experienced a non-significant improvement by follow-up 1 and then returned to baseline by follow-up 2 (p < .04). We found no significant group difference for changes in total intake relative to girls' daily energy needs (p's ≥ .25). However, IPT reduced, while HE increased, the percentage of daily energy needs consumed from snack-foods by follow-up 2 (p = .04). Within-groups, HE increased their snack food intake from follow-up 1 to follow-up 2 (p = .01). CONCLUSIONS: In adolescent girls with LOC, IPT did not change total intake at the test meal and was associated with reduced snack-food intake. Data are required to determine if IPT effectively prevents excess weight gain in the longer-term. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:490-498).

Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.

Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E2 ) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERß estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT2C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E2 , respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards.

Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption.

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds.

Associations of reward sensitivity with food consumption, activity pattern, and BMI in children.

In the current study, the associations of reward sensitivity with weight related behaviors and body mass index were investigated in a general population sample of 443 Flemish children (50.3% boys) aged 5.5-12 years. Cross-sectional data on palatable food consumption frequency, screen time, physical activity, parental education level and measured length and weight were collected. The Drive subscale of the 'Behavioral Inhibition Scale/Behavioral Activation Scale' was used as a short method to measure reward sensitivity. A significant positive association of reward sensitivity with the fast food and sweet drink consumption frequency was found. Furthermore, a significant positive association of reward sensitivity with the z-score of body mass index was demonstrated, which explained additional variance to the variance explained by palatable food consumption frequency, screen time, physical activity and parental education level. Hence, the assessment of reward sensitivity may have an added value to the assessment of weight-related behavior indicators when evaluating the determinants of overweight in a child. In sum, children high in reward sensitivity might be more attracted to fast food and sweet drinks, and hence, might be more vulnerable to develop unfavorable food habits and overweight. These findings suggest that considering inter-individual differences in reward sensitivity is of importance in future childhood obesity prevention campaigns.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 µA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 µA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation.