Document Detail

Animal Models of Compulsive Eating Behavior.
Jump to Full Text
MedLine Citation:
PMID:  25340369     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.
Authors:
Matteo Di Segni; Enrico Patrono; Loris Patella; Stefano Puglisi-Allegra; Rossella Ventura
Related Documents :
22364219 - Presence of nano-sized silica during in vitro digestion of foods containing silica as a...
2166729 - Factors that determine rates of cyanogenesis in bovine ruminal fluid in vitro.
24003139 - Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food...
25405959 - Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems.
10763379 - Excretion of eimeria alabamensis oocysts in grazing calves and young stock.
23578759 - Allured or alarmed: counteractive control responses to food temptations in the brain.
25308539 - Sustainable reduction of nasal colonization and hand contamination with staphylococcus ...
15638749 - Regulating the safety of probiotics--the european approach.
22416689 - Effect of sourdough on quality and acceptability of wheat flour tortillas.
Publication Detail:
Type:  REVIEW     Date:  2014-10-22
Journal Detail:
Title:  Nutrients     Volume:  6     ISSN:  2072-6643     ISO Abbreviation:  Nutrients     Publication Date:  2014  
Date Detail:
Created Date:  2014-10-23     Completed Date:  -     Revised Date:  2014-10-24    
Medline Journal Info:
Nlm Unique ID:  101521595     Medline TA:  Nutrients     Country:  -    
Other Details:
Languages:  ENG     Pagination:  4591-4609     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Nutrients
Journal ID (iso-abbrev): Nutrients
Journal ID (publisher-id): nutrients
ISSN: 2072-6643
Publisher: MDPI
Article Information
Download PDF
© 2014 by the authors; licensee MDPI, Basel, Switzerland.
License:
Received Day: 22 Month: 8 Year: 2014
Revision Received Day: 07 Month: 10 Year: 2014
Accepted Day: 10 Month: 10 Year: 2014
Electronic publication date: Day: 22 Month: 10 Year: 2014
collection publication date: Month: 10 Year: 2014
Volume: 6 Issue: 10
First Page: 4591 Last Page: 4609
PubMed Id: 25340369
ID: 4210935
DOI: 10.3390/nu6104591
Publisher Id: nutrients-06-04591

Animal Models of Compulsive Eating Behavior
Matteo Di Segni12
Enrico Patrono3
Loris Patella3
Stefano Puglisi-Allegra12
Rossella Ventura12*
1Dipartimento di Psicologia and Centro “Daniel Bovet”, Sapienza-Università di Roma, Piazzale Aldo Moro 5, 00181 Roma, Italy; E-Mails: matteodisegni@gmail.com (M.D.); stefano.puglisi-allegra@uniroma1.it (S.P.-A.)
2IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, 00143 Roma, Italy
3Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, University of L’Aquila, via Vetoio (Coppito 2) Coppito, 67010 L’Aquila, Italy; E-Mails: e.patrono@gmail.com (E.P.); lorispatella@gmail.com (L.P.)
These authors contributed equally to this work.
*Author to whom correspondence should be addressed; E-Mail: rossella.ventura@uniroma1.it; Tel.: +39-06-501-703-075.

1. Introduction

Substance use disorders have been extensively studied in recent years, and several lines of evidence suggest that these disorders consist of neuroadaptative pathologies. Addiction is the behavioral outcome of pharmacological overstimulation and the resulting usurpation of neural mechanisms of underlying reward, motivated learning, and memory [1,2]. Although substances such as alcohol, cocaine, and nicotine are extremely popular and central to the study of addiction and substance use disorders, interest is growing in the study of compulsive activities not currently characterized as substance use disorders. One such activity is compulsive overeating [3,4,5,6,7,8].

The apparent loss of control over drug intake and compulsive drug-seeking behavior despite its negative consequences are hallmarks of drug addiction and substance use disorders [9,10,11,12]. However, addictive behaviors are not limited to drug abuse, and a growing body of evidence suggests that overeating and obesity are medical conditions that share several mechanisms and neural substrates with drug intake and compulsive drug-seeking behavior [13,14].

Drug addiction is a chronic, relapsing disorder characterized by an inability to stop or limit one’s drug intake, a strong motivation to take the drug (with activities focused on procuring and consuming the drug), and the continued use of the drug despite harmful consequences [9,12].

Many behavioral parameters of drug addiction have been recapitulated in animal models of drug addiction [9,12]. Some of these behaviors have also been reported in animal models in response to the consumption of highly palatable foods, thus introducing the notion of “food addiction” [1,7].

A scientific definition of “food addiction” has emerged in recent years, and a growing number of studies using animal models suggest that under certain circumstances, overeating can produce behavioral and physiological changes that closely resemble an addiction-like state [11,15,16,17,18].

It has been suggested that the overconsumption of so-called “refined” foods can be described as an addiction that meets the criteria used to define substance use disorders listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) [19,20]. Moreover, because non-drug addictions share the classical definition of addiction with substance abuse and dependence, which includes engaging in the behavior despite serious negative consequences, a new category called “Addiction and Related Behavior” was proposed by the American Psychological Association prior to the publication of DSM-V; this category should include behavioral addictions as well as addictions to natural rewards [1,7]. Finally, the Yale Food Addiction Scale was recently developed to operationalize food dependence in humans. This scale is based largely on the substance use disorders criteria defined in DSM-IV-TR, and the questions are geared specifically to the intake of highly palatable foods.

A key feature of drug addiction is compulsive use despite adverse consequences [9,10,12]; similar compulsive behavior despite negative consequences also occurs in several eating disorders including binge eating disorder, bulimia nervosa, and obesity [21]. Although there is little evidence of continued food seeking/intake despite its possible harmful consequences (an index of compulsion) in rats [22,23] and mice [24], animal models that have reproduced this behavior indicate that adaptive food seeking/intake can be transformed into a maladaptive behavior under specific experimental conditions. Based on this observation, the major goal of this paper is to review the results derived from animal models of compulsive eating behavior. Although an extended, detailed review of neurobiological and behavioral mechanisms common to drug and food addiction is beyond the scope of this paper, we also will briefly summarize some of the most important findings from studies using animal models of drug and food addiction in order to track, whenever possible, the parallels between naturally and pharmacologically rewarding stimuli.


2. Animal Models: Drugs of Abuse and Food
2.1. Animal Models

A large body of evidence suggests that generating animal models of “food addiction” is feasible, and many studies have used a palatable diet to induce overeating, obesity, binge eating, withdrawal symptoms, and food relapse in animal models [7,15,16,18,20,22,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]. In addition, one study by Avena and colleagues (2003) suggests that sugar-bingeing rats develop cross-sensitization with some drugs of abuse [40].

Although animal models cannot explain or reproduce all of the complex internal and external factors that influence eating behavior in humans, these models can enable researchers to identify the relative roles of genetic and environmental variables; this allows better control over these variables and provides for the investigation of underlying behavioral, physiological, and molecular mechanisms [11]. Animal models can be used to investigate the molecular, cellular, and neuronal processes that underlie both normal and pathological behavior patterns. Thus, animal models can advance our understanding of the many factors central to the development and expression of eating disorders.

In recent decades, the animal models in preclinical research have contributed significantly to the study of the etiology of several human psychiatric disorders, and these models have provided a useful tool for developing and validating appropriate therapeutic interventions. Inbred mouse strains are among the most commonly available and useful animal models for investigating putative gene-environment interactions in psychiatric disorders. Specifically, inbred mice have been widely used to identify the genetic basis of normal and pathological behaviors, and strain-related differences in behavior appear to be highly dependent on gene-environment interactions [41].

2.2. Compulsive Use despite Negative Consequences
2.2.1. Drugs of Abuse

Many studies have investigated whether compulsive drug use in the face of adverse consequences can be observed in rodents [10,12,22]. Using intravenous self-administration (SA) of cocaine—the most common procedure for the study of voluntary drug intake in laboratory animals—Deroche-Gamonet and colleagues [22] modeled in rats some diagnostic criteria used to perform the diagnosis of addiction in humans (also see Waters et al. 2014 [42]):

  • (i)  The subject has difficulty stopping drug use or limiting drug intake: the persistence of cocaine seeking during a period of signaled non-availability of cocaine has been measured.
  • (ii)  The subject has an extremely high motivation to take the drug, with activities focused on its procurement and consumption. The authors have used a progressive-ratio schedule: the number of responses required to receive one infusion of cocaine (i.e., the ratio of responding to reward) was increased progressively within the SA session.
  • (iii)  Substance use is continued despite its harmful consequences: the persistence of the animals’ response for the drug when the drug delivery was associated with a punishment has been measured.

This study shows that, similar to addiction in humans, addiction-like behaviors in rats can be found only after a prolonged exposure to the drug. Using a “conditioned suppression” paradigm, Vanderschuren and Everitt [12] investigated whether the ability of a footshock-paired conditioned stimulus (CS) to suppress cocaine-seeking behavior diminished following a prolonged cocaine self-administration history, thus modeling compulsive drug behavior in rats. They found that cocaine seeking can be suppressed by presentation of an aversive CS, but after extended exposure to self-administered cocaine, drug seeking becomes impervious to adversity. These results indicate that an extended drug-taking history renders drug seeking impervious to environmental adversity (such as signals of punishment).

2.2.2. Food

In recent years accumulating evidence suggests the possibility of modeling food addiction in animals, and different environmental conditions have been used to this end. In the “sugar addiction model” proposed by Avena and colleagues, rats are maintained on daily 12-h food deprivation, followed by 12-h access to a solution (10% sucrose or 25% glucose) and rodent chow [21,29,43,44]. After some days on this treatment, the rats show an escalation in their daily intake and binge on the solution, as measured by an increase in their intake of the solution during the first hour of access. In addition to a binge at the onset of access, the rats modify their feeding patterns by taking larger meals of sugar throughout the access period compared to control animals fed the sugar ad libitum. While modeling the behavioral component of food addiction, intermittent access to a sugar solution induces brain changes that are similar to the effects induced by some drugs of abuse [21,29].

In the limited access model proposed by Corwin, previous or current food deprivation is not used to induce binge-type eating, thus ruling out that the observed effects can be produced by food deprivation procedure. To provoke binge-type eating, the rats are given sporadic (generally 3 times per week), time-limited (generally 1–2 h) access to palatable food, in addition to the continuously available chow [15,45]. As described for binge eating disorder, the limited access model is able to induce binge eating in the absence of hunger [15,16,25]. Moreover, availability of addictive food (but also its shortage with periods of food restriction or dieting) are risk factors for developing eating disorders [46], and recurrent periods of caloric restriction are the strongest predictors of overeating in response to stress [47].

As discussed above, a hallmark feature of drug addiction is compulsive drug use in the face of adverse consequences [9,10,12]; similar compulsive behavior despite negative consequences also occurs in several eating disorder including binge eating disorder, bulimia nervosa, and obesity [21]. Consuming large quantities of palatable foods can indicate an increased motivation for food; however, consuming large quantities of palatable foods despite harmful consequences that result from this behavior (for example, tolerating punishment to obtain the food) is compelling evidence of a pathological food compulsion [23].

Although there is little evidence of continued food seeking/intake despite its possible harmful consequences (an index of compulsion) in rats [22,23] and mice [24], animal models that have reproduced this behavior indicate that adaptive food seeking/intake can be transformed into a maladaptive behavior under specific experimental conditions. An important key indicator of compulsive feeding is the inflexibility of the behavior, which can be assessed by temporally limiting the access to palatable food while the standard food remains available [48]. A flexible response would result in a change to available standard food, whereas an inflexible response would be revealed by neglect of the alternative, available standard food [48].

Rat models of compulsive eating have been used to study obesity and binge eating disorder [22,23,48]. To evaluate the compulsive nature of eating palatable food, these models measure the animal’s motivation to seek and consume palatable foods despite facing potentially harmful consequences. In this paradigm, negative consequences are usually modeled by pairing an unconditioned stimulus (US; e.g., a foot shock) with a conditioned stimulus (CS; e.g., light). After conditioning, the effects of exposure to the CS on palatable food seeking and consumption despite the signaled incoming punishment is measured during a test session; one can also measure the animal’s voluntary tolerance for punishment in order to obtain the palatable food. Different animal models (described below) have been proposed to assess compulsive eating behavior in the face of possible negative consequences.

(1). Johnson and Kenny [22] evaluated compulsive eating in obese male rats and found that extended access to palatable, energy-dense foods (18–23 h per day access to the cafeteria-style diet maintained for 40 consecutive days) induces compulsive-like behavior in obese rats (measured by the consumption of palatable food despite the application of a negative CS during a daily 30-min session of access in an operant chamber for 5–7 days). Moreover, they found that D2 dopamine receptors were down-regulated in the striatum of obese rats, a phenomenon that has also been reported in drug-addicted humans, supporting the presence of addiction-like neuroadaptive responses in compulsive eating.

(2). In another study, Oswald and colleagues [23] investigated whether binge eating-prone (BEP) rats, selected on the basis of a stable increase (40%) in consumption of palatable food during a 1–4 h period of time, are also prone to compulsively eating palatable foods. The heightened (i.e., aberrant) motivation for palatable food was measured as the animal’s increase in voluntary tolerance for punishment in order to obtain a particular palatable food (in this case, M & M candies). Their results showed that BEP animals consumed significantly more M & Ms—and tolerated higher levels of foot shock in order to retrieve and consume those candies—than BER (binge eating-resistant) animals. This behavior emerged despite the fact that the BEP rats were sated and could choose to consume standard, shock-free chow in an adjacent arm of the maze. Together, these results confirm that BEP rats have strikingly increased motivation to consume palatable foods.

(3). Using a novel paradigm of conditioned suppression in mice, our group investigated whether a prior session of food restriction could reverse the ability of a foot shock-paired CS to suppress chocolate-seeking behavior, thus modeling food-seeking behavior in the presence of harmful consequences in mice [24].

In a recent experiment (unpublished data, [49]), we used this conditioned suppression paradigm to probe the role of gene-environment interactions in the development and expression of compulsion-like eating behaviors in mice. Thus, by modeling the inter-individual variability that characterizes clinical conditions, we found that genetic background plays a critical role in an individual’s susceptibility to develop aberrant eating behavior, thus supporting the point of view that food-related psychiatric disorders arise from a tight interaction between environmental and genetic factors.

(4). To examine the behavioral drive for dietary reinstatement after withdrawal (W), Teegarden and Bale [28] developed a reinstatement paradigm based on accessibility to the highly preferred high-fat (HF) diet in an aversive arena in mice subjected to withdrawal condition from the HF diet. In this paradigm, mice were required to endure an open, brightly lit environment to reinstate a HF diet despite the availability of house chow (less palatable food) in a less aversive setting. They found that HF-W mice spent more time on the bright side in the presence of a HF pellet in comparison with the mice in the HF non-withdrawal condition or low-fat diet control group. These results strongly demonstrated that an elevated emotional state (produced after preferred-diet reduction) provides sufficient drive to obtain a more preferred food in the face of aversive conditions, despite availability of alternative calories in the safer environment. Their data indicate that, similar to the case of an addict who is in withdrawal from a rewarding substance, mice can show risk-taking behavior to obtain a highly desirable substance.

Based on the observation that an important key indicator of compulsive feeding is the inflexibility of the behavior, Heyne and colleagues have developed a new experimental procedure to assess the inflexible nature of feeding in an animal model of compulsive food-taking behavior in rats [48]. Eating behavior has been assessed by temporally limiting the access to palatable food while the standard food was available. When rats were given a choice between standard food and a highly palatable chocolate-containing diet, they developed an inflexible food-taking behavior, as revealed by neglect of the alternative, available standard food [48].

2.2.3. Withdrawal from Food

Food addiction is currently characterized by food craving, risk of relapse, withdrawal symptoms, and tolerance [7]. Two of the hallmarks of substance dependence are the emergence of withdrawal symptoms upon the discontinuation of drug use and drug craving [37]. Many different laboratories, using different animal models of food addiction (sugar-model, fat-model, and sweet-fat model [7,37]) have investigated the effects of forced abstinence from palatable food on behavior in mice and rats, by first providing animals with long-term access to palatable food and then replacing this food with standard food. However, conflicting results have been reported depending on the kind of food (sugar, fat, sweet-fat) used in different experiments [7].

Using an animal model of binge eating sugar, Avena and colleagues found that when administered the opioid antagonist naloxone, rats showed somatic signs of withdrawal [29]. Similarly, Colantuoni and colleagues [43] investigated withdrawal induced by sugar deprivation and by the administration of naloxone, which increased withdrawal symptoms (teeth chattering, forepaw tremors, head shaking) in rats fed with glucose and ad libitum chow, similarly to rat models of morphine addiction. Behavioral and neurochemical signs of opiate-like withdrawal have also been reported in rats with a history of binge eating sugar without the use of naloxone [50]. Moreover, a high-sugar diet has been shown to elicit signs of anxiety and hyperphagia [51], and cessation of sucrose or glucose availability induced withdrawal-like states, with increased anxiety on the plus-maze [52].

In contrast to sugar-bingeing models, withdrawal-associated symptoms have not been reported using fat-bingeing models. In fact, after 28 days on the assigned high-fat diet, spontaneous restriction and naloxone-precipitated withdrawal did not increase anxiety in the elevated plus-maze or withdrawal-induced somatic behaviors and signs of distress [17,53,54].

Finally, many studies have used a sweet-fat diet (“cafeteria-diet”) comprising diverse highly palatable foods, thus reflecting the availability and diversity of foods available to humans [7]. Using a fat-sweet diet, Teegarden and Bale [28] showed that acute withdrawal from this diet increased anxiety-like behavior, weight loss, and locomotor activity. Similar results were observed in different studies in which withdrawal from the preferred diet induced hypophagia, weight loss, and increased anxiety-like behavior in elevated plus-maze and psychomotor arousal [35,55]. Studies based on the sweet-fat diet investigated many different aspects of food withdrawal, such as the magnitude of withdrawal signs following food deprivation [56] and the role of stress and anxiety as risk factors for relapse and withdrawal symptoms [7,28].

2.3. Common Neurobiological Basis of Drug and Food Addiction

In addition to the above-mentioned behavioral criteria, several brain studies also support the notion that overconsumption of certain foods has several corollaries with drug addiction [54,57]. Brain areas of the reward system are involved in the reinforcement of both food and drugs through dopamine, endogenous opioid, and other neurotransmitter systems, thus suggesting that natural and pharmacological stimuli activate at least some common neural systems [58,59,60,61,62,63,64,65]. The neurocircuitry underlying food and dug addiction is complex and a review of this topic is beyond the scope of this paper. Detailed reviews of this topic can be found elsewhere [6,18,37,38,57,66].

Overall, many reviews have identified a connection between the neural circuits that are recruited while seeking/ingesting palatable food and the circuits activated while seeking/taking drugs of abuse, indicating a common profile of elevated activation in subcortical reward-related structures in response to both naturally and pharmacologically rewarding stimuli or associated cues, and a reduction in activity in cortical inhibitory regions [21,57,66,67,68]. Indeed, it appears that under different access conditions, the potent reward-inducing capacity of palatable foods can drive behavioral modification through neurochemical alterations in brain areas linked to motivation, learning, cognition, and decision making that mirror the changes induced by drug abuse [29,31,33,57,59,64,69,70]. In particular, the changes in the reward, motivation, memory, and control circuits following repeated exposure to palatable food is similar to the changes observed following repeated drug exposure [57,71]. In individuals who are vulnerable to these changes, consuming high quantities of palatable food (or drugs) can disrupt the balance between motivation, reward, learning, and control circuits, thereby increasing the reinforcing value of the palatable food (or drug) and weakening the control circuits [71,72].

Neurobiological Basis of Compulsion-Like Behavior

The best-established mechanism common to both food consumption and drug intake is activation of the brain’s dopaminergic reward circuitry [58,71,72]. The primary sites of these neuroadaptations are believed be the dopamine (DA), mesolimbic, and nigrostriatal circuits. The psychostimulant-induced elevation of extracellular DA levels and stimulation of DA transmission in the mesolimbic circuit is a well-known neurochemical sequence that parallels the effects of a high intake of calorie-rich palatable foods and intermittent sucrose access on activating the brain’s reward system [29,73].

Repeated stimulation of DA reward pathways is believed to trigger neurobiological adaptations in various neural circuits, thus making seeking behavior “compulsive” and leading to a loss of control over one’s intake of food or drugs [71,72]. In addition, the extent of DA release seems to be correlated with both drug-related and food-related subjective reward in humans [70,72]. Repeated stimulation of the DA system by repeated exposure to addictive drugs induces plasticity in the brain, resulting in compulsive drug intake. Similarly, repeated exposure to palatable foods in susceptible individuals can induce compulsive food consumption through the same mechanisms [29,57,64], and neuroimaging studies of obese subjects have revealed changes in the expression of DA receptors reminiscent of the changes found in drug-addicted subjects [58,64,72]. Accordingly, both cocaine addicts and obese subjects have decreased striatal D2 dopamine receptor availability, and this decrease is directly correlated with reduced neural activity in the prefrontal cortex [14,72,74]. Moreover, a growing body of evidence suggests that striatal D1 and D2 dopamine receptors (D1R, D2R) play important roles in motivated behavior [75,76,77,78,79,80,81,82].

Many factors—including the amount of effort an individual is willing to invest to receive a reward and the value that the individual places on the reward—can induce changes in motivated behavior [76,77,78,79,80], and these motivation-related factors are dependent upon dopaminergic transmission in the ventral striatum via D1R and D2R dopamine receptors. Some studies have suggested that optimal goal-directed behaviors and motivation are correlated with increased D2R expression in the striatum [80,83,84,85]. Although striatal DA transmission has been investigated extensively in recent years, the role of DA receptors in the striatum in both normal and pathological food-related motivation remains poorly understood. Nevertheless, the overconsumption of palatable foods has been shown to down-regulate dopaminergic reward circuitry through the same mechanisms that are affected in drug addiction; specifically, in humans the availability of striatal D2R dopamine receptors and DA release are reduced [71,72], leading to the hypothesis (investigated with human and animal models studies) that reduced D2R expression in the striatum is a neuroadaptive response to the overconsumption of palatable food [22,74,86,87]. On the other hand, several studies have also indicated that reduced D2R expression in the striatum may act as a causative factor, predisposing both animals and humans to overeating [22,71,87,88,89].

According to the latest hypothesis, the A1 allele of the DRD2/ANKK1 Taq1A polymorphism is strongly correlated with reduced D2R availability in the striatum, comorbid substance use disorder, obesity, and compulsive behavior [89,90]. In addition, D2R receptors were recently reported to play a critical role in ameliorating binge eating behavior in patients [6], potentially providing a target for treating some eating disorders. More studies are clearly needed to further investigate this promising therapeutic option.

Aside from the striatum, a considerable body of evidence suggests that the prefrontal cortex (PFC) plays a key role in behavioral and cognitive flexibility, as well as in motivated food-related behavior in both animals and humans [62,66,69,72,91,92]. Several areas of the PFC have been implicated in driving the motivation to eat [72,93], and several animal and human studies suggest that the PFC plays a critical role in motivated behaviors related to both food and drugs [33,58,62,69,91,92]. An abundance of data deriving from both animal and human studies suggests that PFC function is impaired in both drug addicts and food addicts [10,66,71,94]. Understanding how these dysfunctional regions in the PFC are involved in emotional processing [95] and inhibitory control [96] is particularly important for understanding addiction.

Taken together, these data show that some prefrontal regions represent a neurobiological substrate common to the drive to eat and take drugs. Functional abnormalities in these regions may enhance either drug-oriented or food-oriented behavior, depending on the established habits of the subject [58], thus leading to compulsion-like behavior.

It has been hypothesized that the transition in behavior—from initially voluntary drug use, to habitual use, and ultimately to compulsive use—represents a transition (at the neural level) in control over drug-seeking and drug-taking behaviors from the PFC to the striatum. This transition also involves a progression shift in the striatum from ventral areas to more dorsal areas, which are innervated—at least in part—by stratified dopaminergic inputs [10,97]. This progressive transition from controlled use to compulsive use seems to be correlated with a shift in the balance of behavioral control processes from the PFC to the striatum [10]. The availability of striatal D2R receptors in obese subjects is correlated with glucose metabolism in some frontal cortical areas, such as the dorsolateral PFC, which plays a role in inhibitory control [72]. Moreover, reduced dopaminergic modulation from the striatum has been suggested to impair inhibitory control over food intake and to increase risk of overeating in humans [11,71,72]. The same direct correlation between striatal D2R availability and glucose metabolism has been reported in the dorsolateral cortex of alcoholics [72].

Prefrontal DA and norepinephrine (NE) transmission has been shown to play a critical role in food-related motivation [62,71,72,98,99], as well as in the behavioral and central effects of drugs of abuse [100,101,102,103,104,105,106] in both animal models and clinical patients. Moreover, prefrontal DA and NE transmission modulate DA transmission in the nucleus accumbens under various experimental conditions [102,103,107,108,109]. In particular, altered D2R expression in the PFC has been associated with certain eating disorders and with drug addiction [14,71,72], and both α1 adrenergic receptors and D1R dopamine receptors have been suggested to play a role in regulating dopamine in the nucleus accumbens [102,103,107,108,109].

Finally, we recently investigated the role of prefrontal NE transmission in maladaptive food-related behavior in a mouse model of chocolate compulsion-like behavior [24]. Our results show that food-seeking behavior in the face of harmful consequences was prevented by selective inactivation of noradrenergic transmission, suggesting that NE in the PFC plays a critical role in maladaptive food-related behavior. These findings point to a “top-down” influence on compulsive behavior and suggest a new potential target for treating some eating disorders. Nevertheless, further research is needed in order to determine the specific role of selective prefrontal dopaminergic and noradrenergic receptors in compulsion-like eating behaviors.

2.4. Environmental Factors Affecting Food Addiction

Eating disorders are multifactorial conditions caused by environmental factors, genetic factors, and the complex interactions between genes and the environment [110,111]. Among the many environmental factors that can influence eating disorders such as obesity, binge eating, and bulimia, the availability of palatable foods is the most obvious [58]. The prevalence of eating disorders has increased during a time when the availability of low-cost, high-fat, high-carbohydrate foods has changed dramatically [58,112]. In fact, significant changes in the food environment have occurred and behaviors that were favored under conditions of food scarcity have become a risk factor in societies where high-energy and highly refined foods are prevalent and affordable [58]. Based on this observation, examining the addictive potential of highly processed foods has become an important goal [112,113].

In addition to quantitative aspects, the quality of the reinforcer is another critical factor for understanding food addiction and eating disorders [58]. It has been shown how different foods induce different levels of compulsive behavior [7,20,58]. In particular, palatable substances such as processed foods containing high levels of refined carbohydrates, fat, salt, and/or caffeine are hypothesized to be potentially addictive [20]. This hypothesis could explain why many people lose their ability to control their intake of such palatable foods [20]. Among palatable foods, animal studies have found that chocolate has particularly strong rewarding properties [62,114,115], as measured by both behavioral and neurochemical parameters, and chocolate is the food that is most often associated with reports of food craving in humans [116]. As a result, chocolate craving and addiction have been proposed in humans [117].

Another important environmental factor in the development and expression of eating disorders is stress. Because stress is one of the most potent environmental drivers of psychopathology, it can play a central role in eating disorders in both animals and humans [58,118,119,120,121]. Indeed, stress affects the development, course, and outcome of several psychiatric disorders, and can influence their recurrence and/or relapse after periods of remission [122,123,124,125,126,127,128,129,130]. Based on research regarding eating disorders, we now understand that stress can perturb the ability to regulate both the qualitative and quantitative aspects of food intake. Assessing stressful conditions that increase one’s susceptibility to developing an eating disorder is one of the primary goals of preclinical eating disorder research. Although both acute and chronic stress can influence food intake (as well as one’s propensity to take drugs of abuse) [58], chronic stress has been shown to increase the consumption of certain palatable foods (i.e., foods that are commonly referred to as “comfort foods”) in both animals and humans [119,130,131], and chronic stress can precipitate binge eating [46,132]. Finally, several groups have reported a synergistic relationship between stress and caloric restriction in promoting the onset of eating disorders—including binge eating—in both humans and animals [11,26,27,120,121].


3. Conclusions

In industrialized nations, overeating is a significant problem, and overeating—particularly overeating palatable foods—leads to increased weight, obesity, and a plethora of related conditions. The continued rise in the prevalence of these conditions has prompted extensive research designed to understand their etiology, and the results of this important, ongoing research have led to policy changes in an attempt to curtail this growing problem [112].

Compulsive eating despite negative consequences is prevalent among patients who suffer from eating disorders such as bulimia nervosa, binge eating disorder, and obesity. Moreover, this behavior is strikingly similar to the phenomenon observed in individuals with compulsive drug-seeking/intake behavior. Because the increasingly compulsive use of drugs in the face of well-known detrimental consequences is a classic behavioral feature of drug addiction, it has been suggested that compulsive overeating—particularly overeating of refined foods—should be classified as a bona fide addiction (i.e., “food addiction”). Indeed, such behavior satisfies the DSM-IV-TR diagnostic criteria for substance use disorders [20], and the Yale Food Addiction Scale, which is currently the most widely used and accepted tool for measuring food addiction [7], was recently developed to operationalize the construct of food addiction, adapting DSM-IV-TR criteria for substance dependence as applied to food [66]. Although these criteria are also present in the new edition of the DSM V (the most recent edition [133]), suggesting that non-substance-related disorders are related to the use of other rewarding stimuli (i.e., gambling), the DSM V does not categorize similar disorders related to natural rewards as behavioral addictions or substance use disorders [7].

Moreover, the literature indicates that food craving frequently results in binge episodes, during which a greater-than-normal quantity of food is ingested in a shorter-than-normal period of time. Importantly, the prevalence of bingeing increases with the body mass index (BMI) and more than one-third of binge-eaters are obese [15]. However, binge eating disorder and food addiction are not correlated with BMI and high BMI is not a predictive factor of compulsive eating [86]. Obesity is a possible, but not obligatory result of compulsive behavior towards food; although the indices of obesity measured by BMI often correlate positively with the index of food addiction measured by the YFAS, they are not synonymous [3,66,134]. This dissociation has been modeled in pre-clinical studies that demonstrate that the development of fat bingeing behavior is not associated with weight gain, supporting the idea that obesity and food addiction are not reciprocal conditions [25,135].

Stressful life events and negative reinforcement can interact with genetic factors, thereby increasing the risk of addictive behaviors and/or inducing changes in the corticostriatal dopaminergic and noradrenergic signals involved in motivational salience attribution processes [62,107,109]. Inbred mouse strains are a fundamental tool for performing genetics studies, and studies comparing different inbred strains have yielded insight into the role that genetic background plays in the dopaminergic system in the midbrain and dopamine-associated behavioral responses [107]. Although they are desperately needed, however, studies of gene-environment interactions in human eating disorders are extremely rare [110]; to date only a handful of animal studies have investigated the specific role of the interaction between environmental factors and genetic factors in the development and expression of compulsive food seeking/intake despite harmful consequences (i.e., an index of compulsion) in rats and mice [22,23,48,136].

Our preliminary data (data not shown, [49]) indicate that compulsive eating emerges following extended access to a highly palatable diet [22], similar to how compulsive drug seeking emerges following an extended history of drug-taking [9,12], but only in genetically susceptible subjects.

Developing well-characterized and validated animal models of compulsive overeating will provide an essential tool for advancing our understanding of the genetic and behavioral factors underlying eating disorders. In addition, these models will facilitate the identification of putative therapeutic targets and help researchers develop, test, and refine suitable pharmacological and cognitive behavioral therapies.


Acknowledgments

This research was supported by Ministero della Ricerca Scientifica e Tecnologica (FIRB 2010; RBFR10RZ0N_001) and “La Sapienza” Grant (C26A13L3PZ, 20013).


Conflicts of Interest

The authors declare no conflict of interest


References
1.. Olsen C.M.. Natural rewards, neuroplasticity, and non-drug addictionsNeuropharmacologyYear: 2011611109112210.1016/j.neuropharm.2011.03.01021459101
2.. Pitchers K.,Balfour M.,Lehman M.. Neuroplasticity in the mesolimbic system induced by natural reward and subsequent reward abstinenceBiol. PsychiatryYear: 20206787287910.1016/j.biopsych.2009.09.03620015481
3.. Avena N.M.,Gearhardt A.N.,Gold M.S.,Wang G.J.,Potenza M.N.. Tossing the baby out with the bath water after a brief rinse? The potential down-side of dismissing food addiction based on limited dataNat. Rev. Neurosci.Year: 20121351410.1038/nrn3212-c122714023
4.. Davis C.,Carter J.C.. Compulsive overeating as an addiction disorder. A review of theory and evidenceAppetiteYear: 2009531810.1016/j.appet.2009.05.01819500625
5.. Davis C.. Compulsive overeating as an addictive behavior: Overlap between food addiction and binge eating disorderCurr. Obes. Rep.Year: 2013217117810.1007/s13679-013-0049-8
6.. Halpern C.H.,Tekriwal A.,Santollo J.,Keating J.G.,Wolf J.A.,Daniels D.,Bale T.L.. Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulationJ. Neurosci.Year: 2013337122712910.1523/JNEUROSCI.3237-12.201323616522
7.. Hone-Blanchet A.,Fecteau S.. Overlap of food addiction and substance use disorders definitions: Analysis of animal and human studiesNeuropharmacologyYear: 201485819010.1016/j.neuropharm.2014.05.01924863044
8.. Muele A.. Are certain foods addictive?Front. PsychiatryYear: 201453824778622
9.. Deroche-Gamonet V.,Belin D.,Piazza P.V.. Evidence for addiction-like behavior in the ratScienceYear: 20043051014101710.1126/science.109902015310906
10.. Everitt B.J.,Belin D.,Economidou D.,Pelloux Y.,Dalley J.,Robbins T.W.. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addictionPhilos. Trans. R. Soc. Lond. B Biol. Sci.Year: 20083633125313510.1098/rstb.2008.008918640910
11.. Parylak S.L.,Koob G.F.,Zorrilla E.P.. The dark side of food addictionPhysiol. Behav.Year: 201110414915610.1016/j.physbeh.2011.04.06321557958
12.. Vanderschuren L.J.,Everitt B.J.. Drug seeking becomes compulsive after prolonged cocaine self-administrationScienceYear: 20043051017101910.1126/science.109897515310907
13.. Berridge K.C.,Ho C.Y.,Richard J.M.,Difeliceantonio A.G.. The tempted brain eats: Pleasure and desire circuits in obesity and eating disordersBrain Res.Year: 20101350436410.1016/j.brainres.2010.04.00320388498
14.. Volkow N.D.,Wang G.J.,Tomasi D.,Baler R.D.. Obesity and addiction: Neurobiological overlapsObes. Rev.Year: 20131421810.1111/j.1467-789X.2012.01031.x23016694
15.. Corwin R.L.,Avena N.M.,Boggiano M.M.. Feeding and reward: Perspectives from three rat models of binge eatingPhysiol. Behav.Year: 2011104879710.1016/j.physbeh.2011.04.04121549136
16.. Hadad N.A.,Knackstedt L.A.. Addicted to palatable foods: Comparing the neurobiology of Bulimia Nervosa to that of drug addictionPsychopharmacologyYear: 20142311897191210.1007/s00213-014-3461-124500676
17.. Kenny P.J.. Common cellular and molecular mechanisms in obesity and drug addictionNat. Rev. Neurosci.Year: 20111263865110.1038/nrn310522011680
18.. Avena N.M.,Bocarsly M.E.,Hoebel B.G.,Gold M.S.. Overlaps in the nosology of substance abuse and overeating: The translational implications of “food addiction”Curr. Drug Abuse Rev.Year: 2011413313910.2174/187447371110403013321999687
19.. American Psychiatric AssociationDiagnostic and Statistical Manual of MentalDisorders4th ed.American Psychiatric PublishingWashington, WA, USAYear: 2010
20.. Ifland J.R.,Preuss H.G.,Marcus M.T.,Rourke K.M.,Taylor W.C.,Burau K.,Jacobs W.S.,Kadish W.,Manso G.. Refined food addiction: A classic substance use disorderMed. HypothesesYear: 20097251852610.1016/j.mehy.2008.11.03519223127
21.. Hoebel B.G.,Avena N.M.,Bocarsly M.E.,Rada P.. Natural addiction: A behavioral and circuit model based on sugar addiction in ratsJ. Addict. Med.Year: 20093334110.1097/ADM.0b013e31819aa62121768998
22.. Johnson P.M.,Kenny P.J.. Addiction-like reward dysfunction and compulsive eating in obese rats: Role for dopamine D2 receptorsNat. Neurosci.Year: 20101363564110.1038/nn.251920348917
23.. Oswald K.D.,Murdaugh D.L.,King V.L.,Boggiano M.M.. Motivation for palatable food despite consequences in an animal model of binge eatingInt. J. Eat. Disord.Year: 20114420321110.1002/eat.2080820186718
24.. Latagliata E.C.,Patrono E.,Puglisi-Allegra S.,Ventura R.. Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic controlBMC Neurosci.Year: 201081115
25.. Corwin R.L.,Buda-Levin A.. Behavioral models of binge-type eatingPhysiol. Behav.Year: 20048212313010.1016/j.physbeh.2004.04.03615234600
26.. Hagan M.M.,Wauford P.K.,Chandler P.C.,Jarrett L.A.,Rybak R.J.,Blackburn K.. A new animal model of binge-eating: Key synergistic role of past caloric restriction and stressPhysiol. Behav.Year: 200277455410.1016/S0031-9384(02)00809-012213501
27.. Boggiano M.M.,Chandler P.C.. Binge eating in rats produced by combining dieting with stressCurr. Protoc. Neurosci.Year: 200610.1002/0471142301.ns0923as36
28.. Teegarden S.L.,Bale T.L.. Decreases in dietary preference produce increased emotionality and risk for dietary relapseBiol. PsychiatryYear: 2007611021102917207778
29.. Avena N.M.,Rada P.,Hoebel B.. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intakeNeurosci. Biobehav. Rev.Year: 200832203910.1016/j.neubiorev.2007.04.01917617461
30.. Le Merrer J.,Stephens D.N.. Food induced behavioral sensitization, its crosssensitization to cocaine and morphine, pharmacological blockade, and effect on food intakeJ. Neurosci.Year: 2006267163717110.1523/JNEUROSCI.5345-05.200616822973
31.. Lenoir M.,Serre F.,Cantin L.,Ahmed S.H.. Intense sweetness surpasses cocaine rewardPLoS OneYear: 20072e69810.1371/journal.pone.000069817668074
32.. Coccurello R.,D’Amato F.R.,Moles A.. Chronic social stress, hedonism and vulnerability to obesity: Lessons from rodentsNeurosci. Biobehav. Rev.Year: 20093353755010.1016/j.neubiorev.2008.05.01818585781
33.. Petrovich G.D.,Ross C.A.,Holland P.C.,Gallagher M.. Medial prefrontal cortex is necessary for an appetitive contextual conditioned stimulus to promote eating in sated ratsJ. Neurosci.Year: 2007276436644110.1523/JNEUROSCI.5001-06.200717567804
34.. Cottone P.,Sabino V.,Steardo L.,Zorrilla E.P.. Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred foodNeuropsychopharmacologyYear: 20083352453510.1038/sj.npp.130143017443124
35.. Cottone P.,Sabino V.,Roberto M.,Bajo M.,Pockros L.,Frihauf J.B.,Fekete E.M.,Steardo L.,Rice K.C.,Grigoriadis D.E.,et al. CRF system recruitment mediates dark side of compulsive eatingProc. Natl. Acad. Sci. USAYear: 2009106200162002019901333
36.. Morgan D.,Sizemore G.M.. Animal models of addiction: Fat and sugarCurr. Pharm. Des.Year: 2011171168117210.2174/13816121179565674721492084
37.. Alsiö J.,Olszewski P.K.,Levine A.S.,Schiöth H.B.. Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeatingFront. Neuroendocrinol.Year: 20123312713910.1016/j.yfrne.2012.01.00222305720
38.. Avena N.M.,Bocarsly M.E.. Dysregulation of brain reward systems in eating disorders: Neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosaNeuropharmacologyYear: 201263879610.1016/j.neuropharm.2011.11.01022138162
39.. Avena N.M.,Gold J.A.,Kroll C.,Gold M.S.. Further developments in the neurobiology of food and addiction: Update on the state of the scienceNutritionYear: 20122834134310.1016/j.nut.2011.11.00222305533
40.. Avena N.M.,Hoebel B.. A diet promoting sugar dependency causes behavioral crosssensitization to a low dose of amphetamineNeuroscienceYear: 2003122172014596845
41.. Cabib S.,Orsini C.,Le Moal M.,Piazza P.V.. Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experienceScienceYear: 200028946346510.1126/science.289.5478.46310903209
42.. Waters R.P.,Moorman D.E.,Young A.B.,Feltenstein M.W.,See R.E.. Assessment of a proposed “three-criteria” cocaine addiction model for use in reinstatement studies with ratsPsychopharmacologyYear: 20142313197320510.1007/s00213-014-3497-224615055
43.. Colantuoni C.,Rada P.,McCarthy J.,Patten C.,Avena N.M.,Chadeayne A.,Hoebel B.G.. Evidence that intermittent, excessive sugar intake causes endogenous opioid dependenceObes. Res.Year: 20021047848810.1038/oby.2002.6612055324
44.. Avena N.M.. The study of food addiction using animal models of binge eatingAppetiteYear: 20105573473710.1016/j.appet.2010.09.01020849896
45.. Corwin R.L.,Wojnicki F.H.. Binge eating in rats with limited access to vegetable shorteningCurr. Protoc. Neurosci.Year: 200610.1002/0471142301.ns0923bs36
46.. Cifani C.,Polidori C.,Melotto S.,Ciccocioppo R.,Massi M.. A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: Effect of sibutramine, fluoxetine, topiramate, and midazolamPsychopharmacologyYear: 200920411312510.1007/s00213-008-1442-y19125237
47.. Waters A.,Hill A.,Waller G.. Bulimics’ responses to food cravings: Is binge-eating a product of hunger or emotional state?Behav. Res. Ther.Year: 20013987788610.1016/S0005-7967(00)00059-011480829
48.. Heyne A.,Kiesselbach C.,Sahùn I.. An animal model of compulsive food-taking behaviourAddict. Biol.Year: 20091437338310.1111/j.1369-1600.2009.00175.x19740365
49.. Di Segni M.Patrono E. (Department of Psychology, UniversityLa Sapienza, Rome). Unpublished work. Year: 2014
50.. Avena N.M.,Bocarsly M.E.,Rada P.,Kim A.,Hoebel B.G.. After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalancePhysiol. Behav.Year: 20089430931510.1016/j.physbeh.2008.01.00818325546
51.. Cottone P.,Sabino V.,Steardo L.,Zorrilla E.P.. Consummatory, anxiety-related and metabolic adaptations in female rats with alternating access to preferred foodPsychoneuroendocrinologyYear: 200934384910.1016/j.psyneuen.2008.08.01018842344
52.. Avena N.M.,Rada P.,Hoebel B.G.. Sugar and fat bingeing have notable differences in addictive-like behaviorJ. Nutr.Year: 200913962362810.3945/jn.108.09758419176748
53.. Bocarsly M.E.,Berner L.A.,Hoebel B.G.,Avena N.M.. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: Implications for nutrient-specific food addiction behaviorsPhysiol. Behav.Year: 201110486587210.1016/j.physbeh.2011.05.01821635910
54.. Kenny P.J.. Reward Mechanisms in Obesity: New Insights and Future DirectionsNeuronYear: 20116966467910.1016/j.neuron.2011.02.01621338878
55.. Iemolo A.,Valenza M.,Tozier L.,Knapp C.M.,Kornetsky C.,Steardo L.,Sabino V.,Cottone P.. Withdrawal from chronic, intermittent access to a highly palatable food induces depressive-like behavior in compulsive eating ratsBehav. Pharmacol.Year: 20122359360210.1097/FBP.0b013e328357697f22854309
56.. Parylak S.L.,Cottone P.,Sabino V.,Rice K.C.,Zorrilla E.P.. Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: Lack of withdrawal-like responsesPhysiol. Behav.Year: 201210723124210.1016/j.physbeh.2012.06.01722776620
57.. Volkow N.D.,Wang G.J.,Fowler J.S.,Telang F.. Overlapping neuronal circuits in addiction and obesity: Evidence of systems pathologyPhilos. Trans. R. Soc. Lond. B Biol. Sci.Year: 20083633191320010.1098/rstb.2008.010718640912
58.. Volkow N.D.,Wise R.A.. How can drug addiction help us understand obesity?Nat. Neurosci.Year: 2005855555615856062
59.. Fallon S.,Shearman E.,Sershen H.,Lajtha A.. Food reward-induced neurotransmitter changes in cognitive brain regionsNeurochem. Res.Year: 2007321772178210.1007/s11064-007-9343-817721820
60.. Kelley A.E.,Berridge K.C.. The neuroscience of natural rewards: Relevance to addictive drugsJ. Neurosci.Year: 2002223306331111978804
61.. Pelchat M.L.. Of human bondage: Food cravings, obsession, compulsion, and addictionPhysiol. Behav.Year: 20027634735210.1016/S0031-9384(02)00757-612117571
62.. Ventura R.,Morrone C.,Puglisi-Allegra S.. Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuliProc. Natl. Acad. Sci. USAYear: 20071045181518610.1073/pnas.061017810417360372
63.. Ventura R.,Latagliata E.C.,Morrone C.,La Mela I.,Puglisi-Allegra S.. Prefrontal norepinephrine determines attribution of “high” motivational saliencePLoS OneYear: 20083e304410.1371/journal.pone.000304418725944
64.. Wang G.J.,Volkow N.D.,Thanos P.K.,Fowler J.S.. Similarity between obesity and drug addiction as assessed by neurofunctional imaging: A concept reviewJ. Addict. Dis.Year: 200423395310.1300/J069v23n03_0415256343
65.. Berner L.A.,Bocarsly M.E.,Hoebel B.G.,Avena N.M.. Pharmacological interventions for binge eating: Lessons from animal models, current treatments, and future directionsCurr. Pharm. Des.Year: 2011171180118710.2174/13816121179565677421492094
66.. Gearhardt A.N.,Yokum S.,Orr P.T.,Stice E.,Corbin W.R.,Brownell K.D.. Neural correlates of food addictionArch. Gen. PsychiatryYear: 20116880881610.1001/archgenpsychiatry.2011.3221464344
67.. Thornley S.,McRobbie H.,Eyles H.,Walker N.,Simmons G.. The obesity epidemic: Is glycemic index the key to unlocking a hidden addiction?Med. HypothesesYear: 20087170971418703288
68.. Trinko R.,Sears R.M.,Guarnieri D.J.,di Leone R.J.. Neural mechanisms underlying obesity and drug addictionPhysiol. Behav.Year: 20079149950510.1016/j.physbeh.2007.01.00117292426
69.. Schroeder B.E.,Binzak J.M.,Kelley A.E.. A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cuesNeuroscienceYear: 200110553554510.1016/S0306-4522(01)00221-411516821
70.. Volkow N.D.,Fowler J.S.,Wang G.J.. The addicted human brain: Insights from imaging studiesJ. Clin. Investig.Year: 20031111444145110.1172/JCI1853312750391
71.. Volkow N.D.,Wang G.J.,Baler R.D.. Reward, dopamine and the control of food intake: Implications for obesityTrends Cogn. Sci.Year: 201115374610.1016/j.tics.2010.11.00121109477
72.. Volkow N.D.,Wang G.J.,Telang F.,Fowler J.S.,Thanos P.K.,Logan J.,Alexoff D.,Ding Y.S.,Wong C.,Ma Y.,et al. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factorsNeuroimageYear: 2008421537154310.1016/j.neuroimage.2008.06.00218598772
73.. Bassareo V.,di Chiara G.. Modulation of feeding-induced activation of mesolimbic dopamine transmission by appetitive stimuli and its relation to motivational stateEur. J. Neurosci.Year: 1999114389439710.1046/j.1460-9568.1999.00843.x10594666
74.. Stice E.,Yokum S.,Blum K.,Bohon C.. Weight gain is associated with reduced striatal response to palatable foodJ. Neurosci.Year: 201030131051310910.1523/JNEUROSCI.2105-10.201020881128
75.. Van den Bos R.,van der Harst J.,Jonkman S.,Schilders M.,Sprijt B.. Rats assess costs and benefits according to an internal standardBehav. Brain Res.Year: 200617135035410.1016/j.bbr.2006.03.03516697474
76.. Flagel S.B.,Clark J.J.,Robinson T.E.,Mayo L.,Czuj A.,Willuhn I.,Akers C.A.,Clinton S.M.,Phillips P.E.,Akil H.. A selective role for dopamine in stimulus-reward learningNatureYear: 2011469535710.1038/nature0958821150898
77.. Berridge K.C.. The debate over dopamine’s role in reward: the case for incentive saliencePsychopharmacologyYear: 200719139143110.1007/s00213-006-0578-x17072591
78.. Salamone J.D.,Correa M.,Farrar A.,Mingote S.M.. Effort-related functions of nucleus accumbens dopamine and associated forebrain circuitsPsychopharmacologyYear: 200719146148210.1007/s00213-006-0668-917225164
79.. Salamone J.D.,Correa M.. The mysterious motivational functions of mesolimbic dopamineNeuronYear: 20127647048510.1016/j.neuron.2012.10.02123141060
80.. Trifilieff P.,Feng B.,Urizar E.,Winiger V.,Ward R.D.,Taylor K.M.,Martinez D.,Moore H.,Balsam P.D.,Simpson E.H.,et al. Increasing dopamine D2 receptor expression in adult nucleus accumbens anhances motivationMol. PsychiatryYear: 2013181025103310.1038/mp.2013.5723711983
81.. Ward R.D.,Simpson E.H.,Richards V.L.,Deo G.,Taylor K.,Glendinning J.I.,Kandel E.R.,Balsam P.D.. Dissociation of hedonic reaction to reward and incentive motivation in an animal model of the negative symptoms of schizophreniaNeuropsychopharmacologyYear: 2012371699170710.1038/npp.2012.1522414818
82.. Baik J.H.. Dopamine signaling in food addiction: Role of dopamine D2 receptorsBMB Rep.Year: 20134651952610.5483/BMBRep.2013.46.11.20724238362
83.. Gjedde A.,Kumakura Y.,Cumming P.,Linnet J.,Moller A.. Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seekingProc. Natl. Acad. Sci. USAYear: 20101073870387510.1073/pnas.091231910720133675
84.. Tomer R.,Goldstein R.Z.,Wang G.J.,Wong C.,Volkow N.D.. Incentive motivation is associated with striatal dopamine asymmetryBiol. Psychol.Year: 2008779810110.1016/j.biopsycho.2007.08.00117868972
85.. Stelzel C.,Basten U.,Montag C.,Reuter M.,Fiebach C.J.. Frontostriatal involvement in task switching depends on genetic differences in D2 receptor densityJ. Neurosci.Year: 201030142051421210.1523/JNEUROSCI.1062-10.201020962241
86.. Colantuoni C.,Schwenker J.,McCarthy J.,Rada P.,Ladenheim B.,Cadet J.L.. Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brainNeuroreportYear: 2001123549355210.1097/00001756-200111160-0003511733709
87.. Stice E.,Yokum S.,Zald D.,Dagher A.. Dopamine-based reward circuitry responsitivity, genetics, and overeatingCurr. Top. Behav. Neurosci.Year: 20116819321243471
88.. Bello N.T.,Hajnal A.. Dopamine and Binge Eating BehaviorsPharmacol. Biochem. Behav.Year: 201097253310.1016/j.pbb.2010.04.01620417658
89.. Stice E.,Spoor S.,Bohon C.,Small D.M.. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 alleleScienceYear: 200832244945210.1126/science.116155018927395
90.. Comings D.E.,Blum K.. Reward deficiency syndrome: Genetic aspects of behavioral disordersProg. Brain Res.Year: 200012632534111105655
91.. Killgore W.D.,Young A.D.,Femia L.A.,Bogorodzki P.,Rogowska J.,Yurgelun-Todd D.A.. Cortical and limbic activation during viewing of high- versus low-calorie foodsNeuroimageYear: 2003191381139410.1016/S1053-8119(03)00191-512948696
92.. Uher R.,Murphy T.,Brammer M.J.,Dalgleish T.,Phillips M.L.,Ng V.W.,Andrew C.M.,Williams S.C.,Campbell I.C.,Treasure J.. Medial prefrontal cortex activity associated with symptom provocation in eating disordersAm. J. PsychiatryYear: 20041611238124610.1176/appi.ajp.161.7.123815229057
93.. Rolls E.T.. Smell, taste, texture, and temperature multimodal representations in the brain, and their relevance to the control of appetiteNutr. Rev.Year: 200462S193S20410.1111/j.1753-4887.2004.tb00099.x15630935
94.. Gautier J.F.,Chen K.,Salbe A.D.,Bandy D.,Pratley R.E.,Heiman M.,Ravussin E.,Reiman E.M.,Tataranni P.A.. Differential brain responses to satiation in obese and lean menDiabetesYear: 20004983884610.2337/diabetes.49.5.83810905495
95.. Phan K.L.,Wager T.,Taylor S.F.,Liberzon I.. Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRINeuroimageYear: 20021633134810.1006/nimg.2002.108712030820
96.. Goldstein R.Z.,Volkow N.D.. Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortexAm. J. PsychiatryYear: 20021591642165210.1176/appi.ajp.159.10.164212359667
97.. Everitt B.J.,Robbins T.W.. Neural systems of reinforcement for drug addiction: From actions to habits to compulsionNat. Neurosci.Year: 200581481148910.1038/nn157916251991
98.. Drouin C.,Darracq L.,Trovero F.,Blanc G.,Glowinski J.,Cotecchia S.,Tassin J.P.. Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiatesJ. Neurosci.Year: 2002222873288411923452
99.. Weinshenker D.,Schroeder J.P.S.. There and back again: A tale of norepinephrine and drug addictionNeuropsychopharmacologyYear: 2007321433145110.1038/sj.npp.130126317164822
100.. Darracq L.,Blanc G.,Glowinski J.,Tassin J.P.. Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamineJ. Neurosci.Year: 199818272927399502830
101.. Feenstra M.G.,Botterblom M.H.,Mastenbroek S.. Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: Effects of novelty and handling and comparison to the nucleus accumbensNeuroscienceYear: 200010074174810.1016/S0306-4522(00)00319-511036208
102.. Ventura R.,Cabib S.,Alcaro A.,Orsini C.,Puglisi-Allegra S.. Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine releaseJ. Neurosci.Year: 2003231879188512629192
103.. Ventura R.,Alcaro A.,Puglisi-Allegra S.. Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbensCereb. Cortex.Year: 2005151877188610.1093/cercor/bhi06615728739
104.. Mingote S,de Bruin J.P.,Feenstra M.G.. Noradrenaline and dopamine efflux in the prefrontal cortex in relation to appetitive classical conditioningJ. Neurosci.Year: 2004242475248010.1523/JNEUROSCI.4547-03.200415014123
105.. Salomon L.,Lanteri C.,Glowinski J.,Tassin J.P.. Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neuronsProc. Natl. Acad. Sci. USAYear: 20061037476748110.1073/pnas.060083910316648258
106.. Wee S.,Mandyam C.D.,Lekic D.M.,Koob G.F.. Alpha 1-noradrenergic system role in increased motivation for cocaine intake in rats with prolonged accessEur. Neuropharm.Year: 20081830331110.1016/j.euroneuro.2007.08.003
107.. Cabib S.,Puglisi-Allegra S.. The mesoaccumbens dopamine in coping with stressNeurosci. Biobehav. Rev.Year: 201236798910.1016/j.neubiorev.2011.04.01221565217
108.. Puglisi-Allegra S.,Ventura R.. Prefrontal/accumbal catecholamine system processes emotionally driven attribution of motivational salienceRev. Neurosci.Year: 20122350952610.1515/revneuro-2012-007623159865
109.. Puglisi-Allegra S.,Ventura R.. Prefrontal/accumbal catecholamine system processes high motivational salienceFront. Behav. Neurosci.Year: 2012273122754514
110.. Bulik C.M.. Exploring the gene-environment nexus in eating disordersJ. Psychiatry Neurosci.Year: 20053033533916151538
111.. Campbell I.C.,Mill J.,Uher R.,Schmidt U.. Eating disorders, gene-environment interactions and epigeneticsNeurosci. Biobehav. Rev.Year: 20103578479310.1016/j.neubiorev.2010.09.01220888360
112.. Gearhardt A.N.,Brownell K.D.. Can food and addiction change the game?Biol. PsychiatryYear: 20137380280322877921
113.. Gearhardt A.N.,Davis C.,Kuschner R.,Brownell K.D.. The addiction potential of hyperpalatable foodsCurr. Drug Abuse Rev.Year: 2011414014521999688
114.. Casper R.C.,Sullivan E.L.,Tecott L.. Relevance of animal models to human eating disorders and obesityPsychopharmacologyYear: 200819931332910.1007/s00213-008-1102-218317734
115.. Ghitza U.E.,Nair S.G.,Golden S.A.,Gray S.M.,Uejima J.L.,Bossert J.M.,Shaham Y.. Peptide YY3–36 decreases reinstatement of high-fat food seeking during dieting in a rat relapse modelJ. Neurosci.Year: 200727115221153210.1523/JNEUROSCI.5405-06.200717959795
116.. Parker G.,Parker I.,Brotchie H.. Mood state effects of chocolateJ. Affect Dis.Year: 20069214915910.1016/j.jad.2006.02.00716546266
117.. Ghitza U.E.,Gray S.M.,Epstein D.H.,Rice K.C.,Shaham Y.. The anxiogenic drugyohimbine reinstates palatable food seeking in a rat relapse model: A role of CRF1 receptorsNeuropsychopharmacologyYear: 2006312188219616341025
118.. Sinha R.,Jastreboff A.M.. Stress as a common risk factor for obesity and addictionBiol. PsychiatryYear: 20137382783510.1016/j.biopsych.2013.01.03223541000
119.. Dallman M.F.,Pecoraro N.,Akana S.F.,la Fleur S.E.,Gomez F.,Houshyar H.,Bell M.E.,Bhatnagar S.,Laugero K.D.,Manalo S.. Chronic stress and obesity: A new view of “comfort food”Proc. Natl. Acad. Sci. USAYear: 2003100116961170110.1073/pnas.193466610012975524
120.. Kaye W.. Neurobiology of anorexia and bulimia nervosaPhysiol. Behav.Year: 20089412113510.1016/j.physbeh.2007.11.03718164737
121.. Adam T.C.,Epel E.S.. Stress, eating and the reward systemPhysiol. Behav.Year: 20079144945810.1016/j.physbeh.2007.04.01117543357
122.. Shaham Y.,Erb S.,Stewart J.. Stress induced relapse to heroin and cocaine seeking in rats: A reviewBrain Res. Rev.Year: 200033133310.1016/S0165-0173(00)00024-210967352
123.. Marinelli M.,Piazza P.V.. Interaction between glucocorticoid hormones, stress and psychostimulant drugsEur. J. Neurosci.Year: 20021638739410.1046/j.1460-9568.2002.02089.x12193179
124.. Charney D.S.,Manji H.K.. Life stress, genes, and depression: Multiple pathways lead to increased risk and new opportunities for interventionsSci. STKEYear: 2004200410.1126/stke.2252004re5
125.. Hasler G.,Drevets W.C.,Manji H.K.,Charney D.S.. Discovering endophenotypes for major depressionNeuropsychopharmacologyYear: 2004291765178110.1038/sj.npp.130050615213704
126.. McFarland K.,Davidge S.B.,Lapish C.C.,Kalivas P.W.. Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behaviorJ. Neurosci.Year: 2004241551156010.1523/JNEUROSCI.4177-03.200414973230
127.. Brady K.T.,Sinha R.. Co-occuring mental and substance use disorders: The neurobiological effects of chronic stressAm. J. PsychiatryYear: 20051621483149310.1176/appi.ajp.162.8.148316055769
128.. Maier S.F.,Watkins L.R.. Stressor controllability and learned helplessness: The role of the dorsal raphe nucleus, serotonin and corticotropin-releasing factorNeurosci. Biobehav.Year: 20052982984110.1016/j.neubiorev.2005.03.021
129.. Dallman M.F.,Pecoraro N.C.,la Fleur S.E.. Chronic stress and comfort foods: Self-medication and abdominal obesityBrain Behav. Immun.Year: 20051927528010.1016/j.bbi.2004.11.00415944067
130.. Pecoraro N.,Reyes F.,Gomez F.,Bhargava A.,Dallman M.F.. Chronic stress promotes palatable feeding, which reduces signs of stress: Feedforward and feedback effects of chronic stressEndocrinologyYear: 20041453754376210.1210/en.2004-030515142987
131.. Fairburn C.G.. Bulimia outcomeAm. J. PsychiatryYear: 1997154179117929396966
132.. Hagan M.M.,Chandler P.C.,Wauford P.K.,Rybak R.J.,Oswald K.D.. The role of palatable food and hunger as trigger factors in an animal model of stress induced binge eatingInt. J. Eat. Disord.Year: 20033418319710.1002/eat.1016812898554
133.. American Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders5th ed.American Psychiatric PublishingArlington, TX, USAYear: 2013
134.. Gearhardt A.N.,Boswell R.G.,White M.A.. The association of “food addiction” with disordered eating and body mass indexEat. Behav.Year: 20141542743310.1016/j.eatbeh.2014.05.00125064294
135.. Rada P.,Bocarsly M.E.,Barson J.R.,Hoebel B.G.,Leibowitz S.F.. Reduced accumbens dopamine in Sprague-Dawley rats prone to overeating a fat-rich dietPhysiol. Behav.Year: 201010139440010.1016/j.physbeh.2010.07.00520643155
136.. Teegarden S.L.,Bale T.L.. Effects of stress on dietary preference and intake are dependent on access and stress sensitivityPhysiol. Behav.Year: 20089371372310.1016/j.physbeh.2007.11.03018155095

Article Categories:
  • Review

Keywords: compulsive eating, animal models, striatum, prefrontal cortex, food addiction.

Previous Document:  Neuropsychiatry and Neural Cubism.
Next Document:  Comparative Study on the Hypoglycemic and Antioxidative Effects of Fermented Paste (Doenjang) Prepar...