Rodent Models of Binge Eating: Are They Models of Addiction?
Rebecca L.W. Corwin and R. Keith Babbs
Abstract
Are recently developed rodent models of binge eating also
models of food addiction? Valid models should meet human
criteria for both bingeing and substance dependence as described in the 4th edition and proposed for the 5th edition of
the Diagnostic and Statistical Manual of Mental Disorders
(DSM). Similarly, behavioral profiles of bingeing animals
should share characteristics with those of animal models of
drug addiction. We evaluate and discuss current rodent models of bingeing, their contributions to scientific understanding of bingeing, their validity with respect to DSM criteria,
and their overlap with models of addiction. The models described indicate that repeated intermittent bouts in which
large quantities of fatty or sugary foods are consumed (binges)
are associated with behavioral changes similar to those described for drugs of abuse. In contrast, control groups consuming the same foods in a nonbinge-type manner do not
exhibit an “addiction-like” behavioral profile. Thus, fatty/
sugary foods in and of themselves do not appear to have
addictive qualities. Rather, the manner in which they are
consumed appears to be critical. In addition, while rodent
models of bingeing and drug self-administration share similarities, we do not support reclassifying the bingeing-related
eating disorders as substance use disorders because of differences that distinguish such disorders in humans.
Key Words: addiction; animal model; behavior; binge;
bulimia; eating disorder; food; rodent
Introduction
I
nterest has recently escalated, both among the lay public
and in the scientific community, in the possibility that
foods may have addictive properties (e.g., Avena 2010;
Blumenthal and Gold 2010; Corsica and Pelchat 2010;
Corwin and Grigson 2009; Dagher 2009; Epstein and
Rebecca L.W. Corwin, RD, PhD, is Professor of Nutritional Neuroscience
in the Nutritional Sciences Department and R. Keith Babbs, MS, is a doctoral student in the Intercollege Graduate Degree Program in Physiology,
both at the Pennsylvania State University College of Health and Human
Development in University Park.
Address correspondence and reprint requests to Dr. Rebecca L.W.
Corwin, Nutritional Sciences Department, The Pennsylvania State
University College of Health and Human Development, 110 Chandlee
Laboratory, University Park, PA 16802 or email [email protected].
Volume 53, Number 1
2012
Shaham 2010; Hetherington and MacDiarmid 1993; Ifland
et al. 2009; Liu et al. 2010; Rogers and Smit 2000; Tuomisto
et al. 1999; Wang et al. 2004). Websites and books provide
forums and solutions to the “problem” of food addiction, and
a television show (Freaky Eaters) is based on the presumed
addictive properties of food. A recent web search for the
term “food addiction” yielded more than a quarter million
hits, and “binge” produced a similarly large number.
But the wealth of information is based on a surprisingly
scant scientific base, in part because animal models of addiction have only recently been described (Koob and Le Moal
2006). The challenge among those who work with laboratory animals (and, indeed, people) has been to develop methods to operationalize addiction. Work with cocaine has
provided guidelines for such operational definitions in rodent models (see Koob and Le Moal 2006 for review); rodent models of binge eating also have been described (e.g.,
Avena et al. 2008; Boggiano et al. 2007; Corwin and BudaLevin 2004; Corwin et al. 2011).
In this review we examine some rodent models of bingeing and determine whether they meet the criteria for addiction as published in the 4th edition and as proposed for the 5th
edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM1; APA 2000, 2012) and as established for
animal models of drug addiction.
What Is Binge Eating?
Binge eating can be characterized both objectively and subjectively. Objectively, it involves the consumption of more
food in a discrete period of time (usually less than 2 hours)
than would normally be consumed in that time under similar circumstances. Thus repeatedly snacking on small quantities of food over a 24-hour period is not characterized
as bingeing by the DSM. Subjectively, bingeing involves
a feeling of lack of control during an eating episode—
individuals report feeling that they cannot stop eating or
that they cannot control the amount or type of food they
consume (APA 2000).
that appear ≥3x throughout this article: BED, binge eating
disorder; BEP, binge eating prone; BER, binge eating resistant; BN,
bulimia nervosa; D, daily; DSM, Diagnostic and Statistical Manual of
Mental Disorders; FR, fixed-ratio; INT, intermittent; PR, progressive
ratio; R-R/S, restriction-refeeding/stress; SVS, sweetened vegetable
shortening
1Abbreviations
23
The DSM includes binge eating in its criteria for bulimia
nervosa (BN1) and binge eating disorder (BED1). In addition, to meet the DSM-IV criteria for BN, the bingeing must
(1) be associated with recurrent inappropriate compensatory
behavior, such as vomiting, fasting, or excessive exercise;
(2) occur at least twice a week for at least 3 months; and (3)
be accompanied by self-evaluation that is unduly influenced
by body image. A change in the binge frequency requirement from twice to once a week has been proposed for the
DSM-V (APA 2012).
To meet the DSM-IV criteria for BED, bingeing must (1)
not be associated with recurrent inappropriate compensatory
behavior, but (2) be associated with at least three of the
following: (a) unusually rapid consumption, (b) eating until
uncomfortably full, (c) eating large amounts of food in the
absence of hunger, (d) eating alone due to embarrassment,
and/or (e) feelings of disgust, depression, or guilt after the
binge; (3) be associated with marked distress about the binge
behavior; and (4) occur, on average, at least twice a week for
at least 6 months. New criteria proposed for inclusion in the
DSM-V are the same as the former criteria with the exception of binge frequency, which has been changed to be the
same as that required for BN (once a week for 3 months)
(APA 2012).
Subthreshold (ST) BED has been provisionally defined
as the occurrence of bingeing at least twice a week for at
least 3 months in the absence of other criteria for BED
(Hudson et al. 2007). Specifically, individuals do not need to
exhibit 3 of the 5 features associated with bingeing nor do
they need to exhibit marked distress about bingeing.
About 1 in 20 Americans engages in binge eating at
some point (Hudson et al. 2007). The 12-month prevalence
is similar to that reported for illicit drug dependence: 2.1%
for binge eating and 2.8% for illicit drug dependence
(Hudson et al. 2007; SAMHSA 2010). Rates of binge eating
are similar in males and females, but the latter are more
likely to be diagnosed with a disorder such as BN or BED,
whereas males are more likely to engage in ST bingeing
(Hudson et al. 2007).
Among those who binge approximately 35% are overweight or obese and 76.5% suffer from psychiatric comorbidities such as anxiety (59.5%) or disorders related to mood
(44%), impulse control (40.2%), or substance use (28.7%)
(Hudson et al. 2007). Craving has been associated with
bingeing (e.g., Gendall et al. 1998; Moreno et al. 2009;
White and Grilo 2005), and bingeing coupled with purging
can lead to serious problems in the oral cavity (Lo Russo
et al. 2008). In addition, impairment of role function in the
home, at work, or in one’s personal or social life occurs in
78% of those with BN, 62.6% of those with BED, and 21.8%
of those with ST BED (Hudson et al. 2007).
In short, binge eating is widespread and associated with
comorbidities that make treatment particularly challenging.
Examining similarities between binge eating and addiction
will improve understanding of this public health problem
and thus support the development of effective therapeutic
interventions.
24
Is Bingeing a Form of Addictive Behavior?
Human Evidence
DSM Criteria for Addiction
To meet criteria for substance dependence (addiction) the
DSM-IV requires evidence of three or more of the following
within a 12-month period:
•
•
•
•
•
•
•
tolerance, as shown by either a need for greater amounts
of a substance to achieve the same effect or reduced
effects achieved with the same amount;
withdrawal, as evidenced by either withdrawal symptoms or the use of the same or a similar substance to
relieve or avoid such symptoms;
consumption of the substance in greater amounts or for a
longer period of time than intended;
unsuccessful efforts to reduce or control use of the
substance;
a great deal of time spent seeking, using, or recovering
from the substance;
substance-associated interference with social, occupational, or recreational activities; and/or
maintenance of substance use even if the user is aware that
such use is causing physical or psychological problems.
A diagnosis of physiological dependence requires fulfillment
of one or both of the first two criteria.
The proposed DSM-V category of Substance Use Disorder
(APA 2012) incorporates the DSM-IV criteria and four new
ones:
•
•
•
•
recurrent use resulting in a failure to fulfill role obligations,
recurrent use in physically hazardous situations,
continued use despite recurrent social or personal problems that are exacerbated by effects of the substance, and
craving of the substance or a strong desire to use it.
In addition, the DSM-V specifies measures of severity: the
fulfillment of two or three criteria indicates moderate substance use, four or more indicates severe use.
Binge Eating and the DSM Addiction Criteria
Food is required for life and therefore not considered inherently addictive under normal circumstances.2 In this review we posit that, to meet the criteria for addiction or the
binge-related eating disorders (or any disorder, for that matter),
a person must engage in the defining behavior to a greater
extent than would normally or reasonably be expected. The
question that we explore is whether food should be considered addictive when behaviors directed toward obtaining and
consuming it are abnormal—specifically, when individuals
2Others, however, have argued that withdrawal-like symptoms (e.g., hunger)
occur in the absence of food (e.g., Hebb 1949), and of course efforts to stop
eating generally prove unsuccessful.
ILAR Journal
consume extremely large quantities in brief periods of time,
as during a binge (also see Cassin and von Ranson 2007;
Davis and Carter 2009).
Figure 1 compares the DSM-IV objective and subjective
criteria for an episode of binge eating to related DSM-IV criteria for addiction (substance dependence). The definition of a
binge (ingestion of a larger amount of food than would normally be consumed) maps onto the addiction criterion of consuming larger amounts than intended. Binge episodes also are
accompanied by a sense of loss of control, which similarly
characterizes addiction: efforts to reduce or control intake are
unsuccessful, the addiction interferes with activities, and the
behavior is maintained despite negative consequences. Bingeing thus meets several of the criteria that define addiction.
Similarly, reports indicate that bingeing-related eating disorders meet many of the DSM-IV and DSM-V criteria for
substance dependence and substance use disorder, respectively. As shown in Table 1, based on the DSM-IV (APA 2000)
it could be argued that both BED and BN meet the criteria for
substance dependence (at least three criteria in 12 months).
Specifically, for a diagnosis of BN or BED, an individual must
(1) consume a larger amount of food than intended and maintain the behavior for a longer period of time than intended
(1–2 times per week for 3–6 months); (2) report loss of control
during the binge episode; and (3) maintain the behavior in
spite of negative consequences such as vomiting (and associated dental/oral cavity problems), eating until uncomfortably
full, or feeling disgust, embarrassment, or distress due to
bingeing. If using the severity specifiers proposed for the
DSM-V, then meeting two or three criteria would categorize
BN and BED as moderate substance use, and meeting four or
more criteria (for instance, if a failure to fulfill role obligations
and/or craving were also present), then severe substance use
would be specified. Thus BN and BED, both of which are
characterized by binge eating, could be considered substance
use disorders/addictions according to the DSM.3
Identifying the “Addictive” Substance
If bingeing-related eating disorders are to be considered substance use disorders, one must ask “What is the addictive
substance?”
“Forbidden foods” rich in fat and sugar are often consumed
during a binge (APA 2000; Guertin 1999; Kales 1990) and
might thus be considered the “substance” as opposed to foods
necessary for health (e.g., fruits and vegetables). Indeed, studies
have reported that, among those with BN, 69% of binge episodes involve forbidden foods (whereas only 15% of nonbinge
episodes contain such foods; Kales 1990) and that those with
BN or BED consume a higher percentage of fat in binge meals
compared to nonbinge meals (Alpers and Tuschen-Caffier
2004; Walsh et al. 1989; Yanovski et al. 1992).
Figure 1 Comparision of DSM-IV criteria for a bingle episode to
related DSM-IV criteria for substance dependence (addiction)
Others, however, have noted no difference in percent
macronutrient composition during a binge even though overall
intakes are elevated (Goldfein et al. 1993; Guss et al. 2002;
Raymond et al. 2007). Furthermore, binge episodes can include foods not typically considered forbidden (Allison and
Timmerman 2007; Williamson et al. 1989).
It is therefore difficult to determine in human studies
whether specific foods contribute to the excessive behavior
or the behavior feeds on itself and becomes self-perpetuating.
Rodent Models of Binge Eating: Overview
Operationalizing Binge Criteria
Rodent models of binge eating have emerged based on the
DSM-IV criteria that characterize binge episodes in humans,
including (1) eating more in a discrete period of time than
would (2) normally be consumed under (3) similar circumstances (4) during the same period of time. Two of these
models meet validity criteria for behavioral models of bingetype eating (as described in Corwin and Buda-Levin 2004)
and several others provide evidence for “addiction-like” behavior. The goal of these models is to distinguish binge-type
eating from other forms of consumption characterized by
large bouts (e.g., palatability-induced eating, rebound hyperphagia) and from normal consumption under similar circumstances. Thus, the ideal model operationalizes not only
“binge” but also “normal” consumption.
A human binge occurs within a discrete period of time
(typically several hours), therefore animal models of bingeing
also need to demonstrate large intakes within defined brief
periods. Additionally, the “similar circumstances” criterion
requires that binge and control animals have similar environmental conditions, including similar access to the palatable food.
Because bingeing involves loss of control as well as large intakes, attempts have also been made to distinguish binge-related
from “normal” behavior using measures other than intake.
Description of Five Rodent Models
History of Food Restriction and Stress (Boggiano)
3We
note that the Yale Food Addiction Scale, while not developed to assess
bingeing specifically, appears to be a valid tool for predicting binge-eating
behavior (Gearhardt et al. 2009).
Volume 53, Number 1
2012
The Boggiano model of bingeing uses cycles of energy restriction and refeeding (R-R1) as well as a stress (S) component
25
Table 1 Criteria for substance dependence (DSM-IV) or substance use disorder (DSM-V) as applied to
bulimia nervosa (BN) and binge eating disorder (BED)a
Criteria for substance dependence/ substance use
disorder (addiction)
BN
Larger amounts, longer duration than intended
√b
√
Failure to control use
Continued use despite knowledge of negative effects
√
√ (vomiting, oral cavity problems)
Interference with activities (DSM-IV and V) or failure of role
obligations (DSM-V)
Craving (DSM-V)
Time spent seeking, using, recovering
Recurrent use in physically hazardous conditions (DSM-V)
Recurrent problems caused or exacerbated by substance (DSM-V)
Tolerance
Withdrawal
√ (78%)c
√
√
(uncomfortable
fullness, disgust,
embarrassment,
distress)
√ (62.6%)
√
n.a.d
n.a.
n.a.
n.a.
n.a.
√
n.a.
n.a.
n.a.
n.a.
n.a.
BED
DSM, Diagnostic and Statistical Manual of Mental Disorders
aAll criteria apply to both the DSM-IV and DSM-V unless specified (i.e., criteria marked “DSM-V” are not designated in the DSM-IV).
b√ indicates that the relevant addiction criterion was met. Information in parentheses under a check mark provides more detail. See text for citations of supporting literature.
cPercentage of BN or BED cases with impairment in role functioning
dn.a., published evidence not available
(foot shock) at the end of the final cycle (thus R-R/S1).4 The
model is therefore particularly relevant to reports showing the
contribution of stress to binge behavior in humans (e.g., APA
2000; Harrington et al. 2006). Immediately after the shock
component, palatable food (typically cookies in this model) and
chow are provided for the next 48 hours and intakes are measured at various time points. Rats exposed to the foot shock
stressor consume significantly more of the palatable food at the
2-hour and 24-hour time points than do rats without either foot
shock or a history of restriction (Hagan et al. 2002, 2003).
Many bingeing models use modified versions of this protocol, with changes in the length of each component of the cycle,
the type of binge food, the type of acute stress administered,
and/or the species of rodent (Cifani et al. 2009, 2010; Consoli
et al. 2009; Hancock et al. 2005; Pankevich et al. 2010).
Intermittent Access (Corwin)
The Corwin model does not include energy restriction to
induce bingeing (e.g., Corwin 2004; Corwin et al. 1998;
Dimitriou et al. 2000; Wojnicki et al. 2007, 2008a) but instead
relies on intermittent limited access to a palatable food
(usually vegetable shortening) to drive escalations in intake.
This model bears on the forbidden foods hypothesis of human bingeing, in which the foods that people restrict in their
4Importantly,
although rats in the R-R/S model have a history of energy
deprivation, they are not food-deprived during the assessment of bingeing.
26
diets become the foods on which they binge (e.g., Kales
1990). Because the rats are never food-deprived, the model
also has relevance to eating in the absence of hunger as described for BED (APA 2000).
The Corwin limited access model consists of two groups
of rats with 24/7 ad libitum access to standard chow and
water. One group has limited access to the optional palatable food for a brief period of time every day (D), and the
second for a brief period intermittently (INT; i.e., only on
certain days—usually Monday, Wednesday, and Friday). At
time points greater than 2 weeks, this protocol results in
significantly higher palatable food intake in INT rats relative to D rats. It also produces higher progressive-ratio
(PR1) responding among INT rats working for the palatable
food in operant chambers compared to D rats (Wojnicki et
al. 2010). We note that, although no obvious stressor is used
in this model, it is possible that the INT rats experience a
“stressful” environment: they are housed with rats that receive the palatable food every day and therefore are exposed
to it without getting to eat it (see, for instance, Cifani et al.
2009, 2010).
In addition to the construct and face validity previously
described (Corwin and Buda-Levin 2004), predictive validity is indicated by recent clinical reports. Specifically, the
␥-aminobutyric (GABA)-B agonist baclofen reduced bingetype intake in rats (Buda-Levin et al. 2005) as well as in
open-label and placebo-controlled trials in humans (Broft
et al. 2007; Corwin et al. 2010). Others have used this model
ILAR Journal
with modifications to the optional food provided, the intermittent access schedule, the length of time the palatable food
was available, and the species (Berner et al. 2009; Czyzyk
et al. 2010; Davis et al. 2007; Kinzig et al. 2008; McGee
et al. 2010).
naloxone-induced withdrawal from the palatable food (suggesting opioid dependency), escalation of intake across time,
increased fixed-ratio (FR1) responding, and addiction-like
neuronal changes (see section below, “Is Bingeing a Form of
Addictive Behavior? Rodent Evidence”).
Binge Eating–Prone (BEP) and Binge Eating–Resistant
(BER) Groups (Boggiano)
Limited Access, Food Restriction, and the
Light:Dark Cycle (Bello)
In addition to the R-R/S bingeing model, Boggiano and
colleagues developed a model that separates rats into binge
eating–prone (BEP) and binge eating–resistant (BER)
groups based on palatable food intake during discrete bouts
of exposure (Boggiano et al. 2007; Oswald et al. 2011).
Although there were important differences between the
groups in terms of chow and palatable food intake in the
face of stress and satiety, there seems to be a limitation inherent in this model in that a rat may not be a bingeing animal simply because it is prone to eat large quantities of the
palatable food. As a result, it may not be possible to distinguish a bingeing phenotype. Stated otherwise, bingeing requires the consumption of more food than would normally
be eaten in a short period of time, which does not seem to
be the case in this model since the BEP rats “normally”
consume a large amount of palatable food. However, the
BEP (but not BER) rats did not decrease palatable food intake after stress, ate as much palatable food when sated as
when hungry, and endured shock to obtain the palatable
food, suggesting an addiction-like behavioral profile (see
section below, “Is Bingeing a Form of Addictive Behavior?
Rodent Evidence”).
Bello and colleagues (2009) used a combination of approaches to stimulate binge-type intakes in rats. The animals
have access to sweetened vegetable shortening (SVS1) for 2
hours beginning 2 hours into the dark cycle on 2 noncontiguous days each week. For about 22 hours prior to SVS access,
the rats are food-deprived; on all other days of the week, they
have ad libitum access to chow. Thus, together with intermittent and limited access to a palatable food, this approach
makes use of acute food deprivation and the fact that rats
normally eat during the dark phase of the light:dark cycle
to stimulate intake. As in the Hoebel model, controls have
continuous access to the palatable food or limited access to
chow. Using this approach, Bello and colleagues (2009) reported escalated intake as well as an increase in c-Fos-positive
cells in the caudal hindbrain in the binge rats.
Mild Food Restriction and the
Light:Dark Cycle (Hoebel)
Hoebel and colleagues developed a model (Colantuoni et al.
2002; see also Avena et al. 2008 for review) that uses daily
mild food restriction followed by palatable food presentation
to increase intake of the palatable food (predominantly sugar
solutions). Specifically, rats are food-deprived for 12 hours
and then presented with the palatable food 4 hours into the
dark cycle. Thus, in contrast to the Corwin and Boggiano
R-R/S models, the rats receive the palatable food during a
period of food deprivation. This approach has relevance to
bingeing in humans, when binge episodes are interspersed
with periods of energy deprivation (APA 2000). Hoebel and
colleagues found that rats with daily access to the palatable
food had significantly higher 1-hour intake than either rats
that received the palatable food only twice or chow controls
(Rada et al. 2005).
Controls typically used in this model (rats with continuous access to the palatable food or limited access to chow)
do not meet the “similar circumstances” criterion of bingeing. However, the Hoebel model has produced data that
support the idea of addiction-like changes in the behavior
and neurobiology of bingeing animals (Avena et al. 2008):
Volume 53, Number 1
2012
Commonalities among Models
Although the models discussed here have numerous methodological differences, they share important commonalities.
For example, all of them use intermittent access to the palatable food to increase intake of that food. This is important
because continuous access to the palatable food does not satisfy the “discrete period of time” criterion necessary to categorize bingeing; therefore, animals with 24/7 access to the
palatable food are not truly bingeing animals.
Is Bingeing a Form of Addictive Behavior?
Rodent Evidence
Can rodent models of binge eating be considered models of
addiction? Koob has comprehensively reviewed animal
models of addiction, sorting them according to both DSM-IV
criteria for addiction and stages in the addiction process—
binge intoxication, withdrawal/negative affect, and preoccupation/anticipation (craving) (Koob and Le Moal 2006). We
consider these and other addiction-like behaviors that have
been characterized in a number of rodent studies of binge
eating.
Characteristics of Addiction-like Behavior
in Rodents
Researchers have used a variety of approaches to characterize
addiction in rodents, including those that model the two DSM
criteria for physiological dependence (tolerance, withdrawal)
27
as well as more recent work using behavioral measures
that model other DSM criteria for substance dependence.
The overarching goal of much of this work has been to
develop criteria that can distinguish addicted animals from
those that are not addicted, a goal similar to that of the binge
models, which is to distinguish bingeing animals from those
that are not bingeing. The following addiction-like behaviors
have been proposed:
1. escalation of intake across time as a behavioral proxy for
the DSM criterion of taking larger amounts of a substance for a longer duration than intended (Ahmed and
Koob 1998; Koob and Le Moal 2006);
2. responding during periods of signaled nonavailability
and higher intakes during extended sessions as indicators
of the inability to control intake (Deroche-Gamonet et al.
2004);
3. PR performance to model willingness to expend effort to
obtain the substance (Deroche-Gamonet et al. 2004), and
escalation of PR performance across time as an indicator
of addiction (Roberts et al. 2007);
4. endurance of shock to obtain the substance, and continued responding for the substance in the presence of a
conditioned aversive stimulus, to model continued use of
the substance despite aversive consequences (DerocheGamonet et al. 2004; Vanderschuren and Everitt 2004).
One of these reports characterized rats as “addiction-prone”
or “addiction-resistant” depending on how many criteria
were satisfied (Deroche-Gamonet et al. 2004).
Numerous binge eating models have characterized rats
using the addiction-like behaviors described above. (1) Escalation of intake, for instance, is greater in binge rats than
in controls in several of the models described (Bello et al.
2009; Corwin et al. 1998; Rada et al. 2005; Wojnicki et al.
2008b), and bingeing rats also demonstrate escalation of FR
and PR responding (Wojnicki et al. 2006). (2) Reports also
indicate higher intakes during extended sessions (Wojnicki
et al. 2008b) and (3) increased PR responding in binge rats
relative to controls (McGee et al. 2010; Wojnicki et al. 2010).
(3) Increased FR responding after a period of sugar abstinence has been reported in sugar-bingeing rats (Avena et al.
2005). (4) Shock endurance to obtain the substance has been
reported for BEP rats by Oswald and colleagues (2010).
In addition to characterizing addiction-like behavior,
Hoebel and colleagues have reported evidence of both spontaneous and naloxone-precipitated withdrawal in sugarbingeing rats (Colantuoni et al. 2002).
Cross Sensitization as an Additional
Characteristic
Hoebel and colleagues have described locomotor cross sensitization between a sugar solution and amphetamine in
bingeing rats (Avena and Hoebel 2003a,b); similar results
were reported for sugar and cocaine in rats with a history of
limited (1-hour) access to solid sugar (Gosnell 2005).
28
In a subsequent study, Hoebel and colleagues observed
consummatory cross sensitization between sugar and ethanol drinking after a period of sugar abstinence: rats that
binged on sugar took more ethanol during self-administration
sessions, and vice versa (Avena et al. 2004). This phenomenon could be relevant to one of the ways that the DSM
characterizes withdrawal, i.e., the use of a different substance (in this case ethanol) to relieve withdrawal from the
primary substance (in this case sugar). These results also
have relevance to the comorbidity between binge eating and
alcohol abuse or dependence (Hudson et al. 2007).
There also is evidence of consummatory cross sensitization between fat and cocaine after a period of abstinence
from an optional fat source. Rats with a history of bingeing
on fat worked harder for cocaine and responded more often
during periods of signaled cocaine nonavailability than did
rats without the binge history (Puhl et al. 2011). These results bear on the comorbidity between binge eating and illicit drug abuse or dependence (Hudson et al. 2007).
Taken together, the evidence suggests that bingeing, as
operationally defined in all of the foregoing models, could
be considered a form of addictive behavior. Table 2 shows
addiction-like behaviors that have been reported for rodent
binge models and compares them to DSM binge and addiction criteria.
The Role of Incentive Salience
The studies described above show that rats consume and
work for foods rich in fat and/or sugar, but only some of the
rats exhibit an addiction-like profile. Control rats consuming
the same food do not exhibit the same profile. In many cases,
the total cumulative intake of the palatable food is greater in
the controls, even though their intake during the binge period
is lower.
Thus fatty/sugary food in and of itself cannot be considered addictive. It becomes “addictive” only when its incentive salience is enhanced (Berridge et al. 2010), for example
by inherent traits in vulnerable individuals, as evidenced by
the Boggiano BEP/BER model. This model, which provides
a basis for identifying and evaluating individual differences
in intake and addiction-like behavior in rats that consume
palatable food in the same context, shows that BEP rats exhibit
more behavior indicative of an addiction-like profile than BER.
Aside from innate predisposition, environmental context
can enhance the incentive salience of food. In the Corwin
model, for instance, groups are initially matched on intake
and body weight parameters and the contribution of various environmental contexts is then evaluated. A profile of addictionlike behavior is evident mainly in rats with intermittent
(Monday, Wednesday, Friday), limited (~1 hour) access to
the optional fat source, rather than those with daily limited
or continuous (24/7) access.
The same context, however, does not render all foods addictive. Chow intake does not increase when provided under
the same conditions that promote escalation of SVS or
ILAR Journal
Table 2 Addiction-like behavior in rat models of binge eating
DSM binge criteria
DSM addiction
criteria
Rat addictionlike behavior
Corwin
model
Hoebel
model
Boggiano
BEP
model
Large amount, long
duration
Large amount, long
duration
Intake escalation
√a
√
n.a.
Loss of control
Failure to control use
Higher intake with
extended session length
Shock endurance to
obtain substance
Increased PR
√
n.a.
n.a.
n.a.
n.a.
√
√
n.a.
n.a.
√
n.a.
n.a.
n.a.
√
√
√
√
n.a.
n.a.
n.a.
n.a.
√
n.a.
n.a.
Maintenance in spite of
negative consequences
Effort expended to obtain
the substance
Withdrawal
Increased FR
Withdrawal
Locomotor cross-sens
Consummatory
cross-sens (sugar/EtOH)
Consummatory
cross-sens (fat/cocaine)
BEP, binge eating–prone; cross-sens, cross sensitization; DSM, Diagnostic and Statistical Manual of Mental Disorders (criteria from DSM-IV and
proposed DSM-V); EtOH, ethanol; FR, fixed ratio; n.a., no available published evidence; PR, progressive ratio
a√ indicates that bingeing animals in each model exhibited the relevant rat addiction-like behavior.
See text for sources.
sucrose intake (Bello et al. 2009; Rada et al. 2005). Thus, the
rodent models indicate that a highly preferred fatty/sugary
food (i.e., one with high incentive salience) is necessary but
becomes “addictive” only when consumed by vulnerable individuals or in a given context (e.g., limited and intermittent
access).
Role of Environmental Factors in
Binge Eating
As illustrated above, both innate and environmental factors
can affect susceptibility to binge eating. Genetic traits that
enhance the incentive salience of food and render individuals vulnerable to binge eating or “food addiction” are under
intense investigation, but unequivocal results have not yet
been reported (Scherag et al. 2010). Models such as BEP/
BER will likely prove important to understanding genetic
and other traits that contribute to individual differences.
Rodent models can also provide insight into state differences by characterizing the environmental conditions—
periodic energy deprivation, intermittent access, and stress—
that enhance the incentive salience of food and promote
binge eating. In addition to these factors, we consider the
macronutrients consumed during the binge.
Energy Deprivation
Periodic energy deprivation (dieting) is associated with
binge eating (APA 2000) and included in several rodent
Volume 53, Number 1
2012
models of binge eating. Such models (with appropriate controls for deprivation) may effectively model the influence of
either a history of dieting (e.g., Hagan et al. 2002, 2003) or
current dieting (e.g., Avena et al. 2008; Bello et al. 2009) on
palatable food intake and associated physiological and neurological mechanisms. Of relevance to addiction studies in
general is the well-known stimulatory effect of energy deprivation on drug self-administration in animals (see Carr 2007
for review).
Energy deprivation may contribute to bingeing for
reasons other than, or in addition to, hunger. For instance,
mice with a history of energy restriction exhibited (1) elevated hypothalamic levels of the orexigenic hormones
melanocortin-concentrating hormone and orexin, (2) reduced corticotropin-releasing factor in the bed nucleus of the
stria terminalis, and (3) binge-type consumption of a highfat diet in response to chronic unpredictable variable stress.
These effects were evident after refeeding, indicating the
long-term influence of energy restriction on hormonal responsiveness and behavior (Pankevich et al. 2010).
Pairing the availability of palatable food and its associated cues with food deprivation may promote bingeing in a
manner similar to that reported for cue-induced eating (e.g.,
Holland and Petrovich 2005). Rats in cue-potentiated feeding protocols have a history of food deprivation but are
not food-deprived during the intake test, whereas in some
bingeing models they are (e.g., Bello, Hoebel models). To
determine whether cue-potentiated eating contributes to
bingeing in those models, intake tests would need to take
place under non-food-deprived conditions. In contrast to the
29
Bello and Hoebel models, rats in the Boggiano R-R/S model
have a history of energy deprivation but are not deprived during the intake tests. Thus cue-induced feeding may well contribute to bingeing in the R-R/S protocol (but see also
Boggiano et al. 2009 for effects of food-cue pairing without
energy deprivation).
Intermittent Access
All the models described in this review use some form of
intermittent access to the binge food. The R-R/S model provides the palatable food (cookies) for 24–48 hours after a
~10-day restriction-refeeding cycle. Bingeing on the palatable food is assessed at the end of the weight recovery period
(in the absence of food deprivation) in response to an acute
stressor (shock). In the BEP/BER model, the palatable food
(cookies) is provided every 3 to 5 days for 24 hours, in the
Corwin model 1 to 2 hours 3 times a week (generally a solid
fat), in the Hoebel model every day for 12 hours (generally a
sugar solution), and in the Bello model twice a week for 2
hours (SVS). Thus none of the binge groups has continuous
access, a difference that distinguishes the binge models from
diet-induced obesity models and suggests that intermittency
may be important to both bingeing and the expression of
addiction-like behavior.
Studies have similarly shown that intermittency stimulates ethanol and nicotine intake, with bout intake increasing
as bout opportunities decrease (e.g., Corrigal and Coen
1989; Files et al. 1994; Heyser et al. 1997; Marcucella and
Munro 1987; Pinel and Huang 1976; Wayner and Fraley
1972; Wise 1973). This finding accords with reports that intake of the optional palatable food during a discrete bout is
greater in rats with fewer bout opportunities (e.g., Corwin
2004; Corwin et al. 1998; Dimitriou et al. 2000). Furthermore, addiction-like behaviors in this model are exhibited
primarily by rats that get the optional fat three times a week
(see Table 2).
The Hoebel model, on the other hand, entails daily access to palatable food for relatively long periods of time (12
hours). A comparison of results from rats with 30-minute
(short) versus 12-hour (long) access to sugar showed that
only the latter demonstrated increased FR responding after a
period of sugar abstinence (Avena et al. 2005). This finding
corresponds to results reported for cocaine: only rats with
daily periods of relatively long access (6 hours vs. 1 hour)
show behavioral profiles indicative of addiction (Koob and
Le Moal 2006).
Intermittency appears to produce maximal intakes only if
bingeing occurs, not when rats receive small portions during
their access to the palatable substance. In one study (Wojnicki
et al. 2008b), non-food-deprived rats had intermittent
(Monday, Wednesday, Friday) access to a small quantity of palatable food (shortening): bingeing was not possible because
the animals received only 2 g of shortening during the access
period. After 5 weeks of this protocol, the rats were switched
to a standard binge protocol for an additional 5 weeks, during
30
which they could consume as much as desired during the
shortening access period. Intakes during the second 5-week
period were compared to rats that had been maintained on the
standard binge protocol throughout. During the second
5-week period, intakes in the previously small quantity group
were significantly lower than those of the rats that had
binged throughout. This study suggests that intermittent exposure to palatable food under conditions in which intake
is controlled may protect against subsequent intake excess
to some extent.
Why intermittent access to fatty/sugary optional foods
promotes bingeing and addiction-like behavior has not yet
been demonstrated. This is particularly curious since some
models (e.g., Hoebel) report binge-type eating when the palatable food is provided every day, whereas others (e.g.,
Corwin, Bello, Boggiano) report binge-type eating when the
palatable food is provided more infrequently. It is obvious
that the phenotype of bingeing can be expressed under a
wide variety of conditions in rats, which is likely quite similar to what happens in humans.
Stress
Intermittency may contribute to binge eating and addictionlike behavior by engaging the stress axis (Cottone et al.
2009). Reports show that a variety of other stressors—shock
(Hagan et al. 2002, 2003), exposure to palatable food without the opportunity to consume it (Cifani et al. 2009, 2010),
forced swimming (Consoli et al. 2009), chronic variable
stress (Pankevich et al. 2010), and reduced maternal care
early in life coupled with shock (Hancock et al. 2005)—can
powerfully influence palatable food consumption. These
manipulations in rodents are thought to model the contribution of stress to bingeing in humans (APA 2000; Harrington
et al. 2006) and have relevance to the importance of stress in
addiction (Volkow et al. 2010).
Abstinence from palatable foods engages stress systems
(Cottone et al. 2009), which may contribute to overconsumption when the abstinence ends. Consistent with this
idea is research showing reductions in physiological stress
responsivity associated with the consumption of optional fat
and sugar provided either continuously (Pecoraro et al.
2004) or intermittently (Kinzig et al. 2008). Thus, intermittency may not only activate reward-related circuits during
the consummatory act but provoke consumption due to activation of antireward circuits during the abstinent periods
(Cottone et al. 2009). In other words, the aversive state created by the absence of palatable food negatively reinforces
overconsumption of that food (see Koob and Le Moal 2005).
Effects of Macronutrients Consumed During
the Binge
Direct comparisons between fat and sugar have been made
in a few studies and results indicate that solid fats and liquid
sugars have different effects on addiction-related processing.
ILAR Journal
Avena and colleagues (2009), for instance, reported withdrawallike symptoms in rats bingeing on sugar solutions, but not
in rats bingeing on pure fat or fatty foods. In addition, our
group has shown that opioid blockade more potently reduced sucrose intake in bingeing rats than in controls; potency differences were not seen in rats consuming fat
(Corwin and Wojnicki 2009). These results suggest a unique
role for endogenous opioids in sugar bingeing but not in fat
bingeing.
We previously reported effects of various peripherally
administered pharmacological probes in rats bingeing on
sugar solutions and solid fats (Corwin and Wojnicki 2009).
Results from these studies indicate differential involvement
of dopamine D2-like receptors between INT and D rats consuming solid fats but not in INT and D rats consuming sugar
solutions. More recent data suggest that effects in fat-bingeing
rats are at least partially due to changes in prefrontal cortical D2 signaling (Babbs and Corwin 2011; Corwin and
Babbs 2011). Other studies have also shown that dopamine
function is altered in bingeing rats and humans as well as in
other models of compulsive food intake (Bello and Hajnal
2010; Johnson and Kenny 2010; Rada et al. 2005; Wang
et al. 2011).
Finally, the Hoebel and Corwin labs have both reported
differential effects of baclofen in rats bingeing on sugar or
fat (Berner et al. 2009; Corwin and Wojnicki 2009). Specifically, baclofen reduced solid fat intake in fat-bingeing rats
but had no effect on liquid sugar intake in sugar-bingeing
rats. Because baclofen also reduces self-administration of
several drugs of abuse in rats (e.g., Cousins et al. 2002),
these results support an addiction-like interpretation of fat
bingeing in the rat models. In humans baclofen has shown
promise for the treatment of substance dependence (Tyacke
et al. 2010) and binge eating (Broft et al. 2007; Corwin et al.
2010b), again supporting the relevance of the animal work to
the human condition.
Overall, these reports indicate important differences between the effects of fat and sugar when consumed under
binge-type conditions.
Relevance of Intermittent Access in
Rodent Models to Human Intake
Intermittent access in rodent models has relevance to human
binge eaters’ pattern of avoiding specific foods (forbidden
foods) and then consuming them in excess during a binge
(Guertin 1999; Kales 1990). In addition, intermittent access
may engage the stress axis (as discussed above) and provoke
excessive intake due to the uncertainty associated with opportunities to consume the palatable food (Corwin 2011).
In this regard, the rodent models have relevance to chaotic or unstructured food environments common to societies
experiencing food abundance. Families in developed, foodabundant societies often do not sit down together for meals
(Sisson et al. 2011), time spent in food preparation is low
(Jabs and Devine 2006), and consumption of food prepared
Volume 53, Number 1
2012
outside the home has escalated (Guthrie et al. 2002). Such
environments can strongly influence appetitive cognition
(Lowe et al. 2009), can render eating episodes unpredictable,
and may contribute to binge-type excess (Hagan et al. 2002).
The problem is not food scarcity but rather food abundance: people have a multitude of opportunities to eat large
quantities of highly palatable foods, which allows for spontaneous rather than planned eating opportunities. Recent
research indicates that such environments may contribute
to binge eating. Adolescent females who usually ate dinner
with the family were less likely to binge eat relative to adolescent females who rarely ate dinner with the family
(Haines et al. 2010). Thus, structured eating environments
with limited choices appear to protect against binge eating,
not so much because of the types of food that are available
but rather because of the context in which those foods are
provided. Indeed, the establishment of a regular eating
schedule is recommended as part of at least one known effective therapeutic strategy for binge eaters (Murphy et al.
2010).
Conclusions
We have described rodent models of binge eating, many of
which satisfy at least some of the criteria for addiction defined for rodent models of drug self-administration. These
comparisons in animals parallel comparisons we and others
(e.g., Cassin and von Ranson 2007; Davis and Carter 2009;
Gearhardt et al. 2011) have made between human binge eating and addiction as defined by the DSM. The rodent models
indicate that the consumption of certain foods can become
problematic, but only under conditions that promote intermittent bouts of excessive eating.
It is important to remember that control rats consuming
the same, or even greater, amounts of the same food, but in a
different context, do not exhibit addiction-like profiles of behavior. Thus, to label any given food as addictive, without
qualifying the conditions under which problems are likely to
arise, is misleading.
Individual trait differences undoubtedly contribute to
binge-type eating and addiction. However, research using
rodent models of binge eating has provided compelling evidence that state differences induced by environmental conditions also contribute to pathological changes that share
striking similarities to those described for addiction.
Although comparisons between binge eating and addiction may guide research, we urge caution with the use of the
term “food addiction,” particularly in therapeutic settings.
Such a term is difficult to operationalize, leads to semantic
vagueness, and may promote the use of treatment strategies,
such as food avoidance, that could prove ineffective or even
make matters worse. For instance, whereas treatment for
addiction usually requires complete abstinence from the
substance of concern, complete abstinence from food obviously is not possible, and complete abstinence from specific
foods and their associated pervasive cues is a daunting effort, at best. In fact, attempts to avoid food are specifically
31
associated with bingeing and reduced quality of life in humans (Latner et al. 2008).
Moreover, rat models have clearly shown that periodic
energy deprivation (dieting) contributes to binge-type eating
and that abstinence from fatty/sugary foods for even a nonfood-deprived animal can promote bingeing when that food
is subsequently available for consumption. Avoidance of
specific foods is similarly thought to contribute to binge pathology in humans (e.g., Kales 1990), and at least one effective therapeutic approach for BN and BED targets forbidden
foods by systematically reintroducing them into the diet
(Murphy et al. 2010).
For this and other reasons, in spite of similarities between bingeing and addiction, we do not support reclassifying bingeing-related eating disorders as substance use
disorders. Eating disorders already have a DSM designation;
their reclassification as substance use disorders is not necessary. Furthermore, eating disorders are characterized by
unique concerns with body shape and weight that do not
typically characterize substance use disorders (APA 2000;
Cassin and von Ranson 2007).
In summary, rodent models of binge eating provide a
means to evaluate factors that contribute to intermittent
bouts of excessive consumption in a controlled environment.
There is no perfect animal model of the complexities associated with human disordered eating, but animal models can
enhance understanding of a variety of causes and consequences of binge eating and provide preclinical opportunities to test new interventions.
Acknowledgment
The author (Corwin) receives support from the National Institutes of Health (grant RO1 MH67943).
References
Ahmed SH, Koob GF. 1998. Transition from moderate to excessive drug
intake: Change in hedonic set point. Science 282:298-300.
Allison S, Timmerman GM. 2007. Anatomy of a binge: Food environment
and characteristics of nonpurge binge episodes. Eat Behav 8:31-38.
Alpers GW, Tuschen-Caffier B. 2004. Energy and macronutrient intake in
bulimia nervosa. Eat Behav 5:241-249.
APA [American Psychiatric Association]. 2000. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed, text revision (DSM-IV-TR).
Washington.
APA. 2012. DSM-5 Development. Available online (www.dsm5.org/Pages/
Default.aspx), accessed March 15, 2012.
Avena NM. 2010. The study of food addiction using animal models of binge
eating. Appetite 55:734-737.
Avena NM, Hoebel BG. 2003a. A diet promoting sugar dependency causes
behavioral cross-sensitization to a low dose of amphetamine. Neuroscience 122:17-20.
Avena NM, Hoebel BG. 2003b. Amphetamine-sensitized rats show sugarinduced hyperactivity (cross-sensitization) and sugar hyperphagia.
Pharmacol Biochem Behav 74:635-639.
Avena NM, Carrillo CA, Needham L, Leibowitz SF, Hoebel BG. 2004.
Sugar-dependent rats show enhanced intake of unsweetened ethanol.
Alcohol 34:203-209.
32
Avena NM, Long KA, Hoebel BG. 2005. Sugar-dependent rats show enhanced responding for sugar after abstinence: Evidence of a sugar deprivation effect. Physiol Behav 84:359-362.
Avena NM, Rada P, Hoebel BG. 2008. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32:20-39.
Avena NM, Rada P, Hoebel BG. 2009. Sugar and fat bingeing have notable
differences in addictive-like behavior. J Nutr 139:623-628.
Babbs RK, Corwin RL. 2011. Exacerbation of binge eating by inactivation of
the prefrontal cortex. Program No. 600.20. Neuroscience Meeting Planner.
Washington: Society for Neuroscience. Available online (www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=4349c3f9-c312-4e0e-9ab11df1a459ce23&cKey=3c1e3408-f8bb-4665-a490-078f95b8586e&m
Key={8334BE29-8911-4991-8C31-32B32DD5E6C8}).
Bello NT, Hajnal A. 2010. Dopamine and binge eating behaviors. Pharmacol
Biochem Behav 97:25-33.
Bello NT, Guarda AS, Terrillion CE, Redgrave GW, Coughlin JW, Moran TH.
2009. Repeated binge access to a palatable food alters feeding behavior,
hormone profile, and hindbrain c-Fos responses to a test meal in adult
male rats. Am J Physiol Regul Integr Comp Physiol 297:R622-R631.
Berner LA, Bocarsly ME, Hoebel BG, Avena NM. 2009. Baclofen suppresses binge eating of pure fat but not a sugar-rich or sweet-fat diet.
Behav Pharmacol 20:631-634.
Berridge KC, Ho CY, Richard JM, DiFeliceantonio AG. 2010. The tempted
brain eats: Pleasure and desire circuits in obesity and eating disorders.
Brain Res 1350:43-64.
Blumenthal DM, Gold MS. 2010. Neurobiology of food addiction. Curr
Opin Clin Nutr Metab Care 13:359-365.
Boggiano MM, Dorsey JR, Thomas JM, Murdaugh DL. 2009. The Pavlovian power of palatable food: Lessons for weight-loss adherence from a
new rodent model of cue-induced overeating. Int J Obes (Lond) 33:693701.
Boggiano MM, Artiga AI, Pritchett CE, Chandler-Laney PC, Smith ML,
Eldridge AJ. 2007. High intake of palatable food predicts binge-eating
independent of susceptibility to obesity: An animal model of lean vs
obese binge-eating and obesity with and without binge-eating. Int
J Obes (Lond) 31:1357-1367.
Broft AI, Spanos A, Corwin RL, Mayer L, Steinglass J, Devlin MJ, Attia E,
Walsh BT. 2007. Baclofen for binge eating: An open-label trial. Int J Eat
Disord 40:687-691.
Buda-Levin A, Wojnicki FH, Corwin RL. 2005. Baclofen reduces fat intake
under binge-type conditions. Physiol Behav 86:176-184.
Carr KD. 2007. Chronic food restriction: Enhancing effects on drug reward
and striatal cell signaling. Physiol Behav 91:459-472.
Cassin SE, von Ranson KM. 2007. Is binge eating experienced as an addiction? Appetite 49:687-690.
Cifani C, Polidori C, Melotto S, Ciccocioppo R, Massi M. 2009. A preclinical model of binge eating elicited by yo-yo dieting and stressful
exposure to food: Effect of sibutramine, fluoxetine, topiramate, and
midazolam. Psychopharmacology (Berl) 204:113-125.
Cifani C, Micioni Di B MV, Vitale G, Ruggieri V, Ciccocioppo R, Massi M.
2010. Effect of salidroside, active principle of Rhodiola rosea extract,
on binge eating. Physiol Behav 101:555-562.
Colantuoni C, Rada P, McCarthy J, Patten C, Avena NM, Chadeayne A,
Hoebel BG. 2002. Evidence that intermittent, excessive sugar intake
causes endogenous opioid dependence. Obes Res 10:478-488.
Consoli D, Contarino A, Tabarin A, Drago F. 2009. Binge-like eating in
mice. Int J Eat Disord 42:402-408.
Corrigal WA, Coen KM. 1989. Nicotine maintains robust self-administration
in rats on a limited access schedule. Psychopharmacology (Berl) 99:
473-478.
Corsica JA, Pelchat ML. 2010. Food addiction: True or false? Curr Opin
Gastroenterol 26:165-169.
Corwin RL. 2004. Binge-type eating induced by limited access in rats
does not require energy restriction on the previous day. Appetite
42:139-142.
Corwin RL. 2011. The face of uncertainty eats. Curr Drug Abuse Rev
4:174-181.
ILAR Journal
Corwin RL, Babbs RK. 2011 Exacerbation of binge eating by blockade of
prefrontal cortical D2 receptors. Program No. 600.21. Neuroscience
Meeting Planner. Washington: Society for Neuroscience. Available
online (www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=
4349c3f9-c312-4e0e-9ab1-1df1a459ce23&cKey=5512d8db-d81e48e5-b7a3-feb919a077fd&mKey={8334BE29-8911-4991-8C3132B32DD5E6C8}).
Corwin RL, Buda-Levin A. 2004. Behavioral models of binge-type eating.
Physiol Behav 82:123-130.
Corwin RL, Grigson PS. 2009. Symposium overview—Food addiction:
Fact or fiction? J Nutr 139:617-619.
Corwin RL, Wojnicki FH. 2009. Baclofen, raclopride, and naltrexone differentially affect intake of fat and sucrose under limited access conditions. Behav Pharmacol 20:537-548.
Corwin RL, Avena NM, Boggiano MM. 2011. Feeding and reward: Perspectives from three rat models of binge eating. Physiol Behav 104:
87-97.
Corwin RL, Wojnicki FH, Fisher JO, Dimitriou SG, Rice HB, Young MA.
1998. Limited access to a dietary fat option affects ingestive behavior
but not body composition in male rats. Physiol Behav 65:545-553.
Corwin RL, Boan J, Peters K, Walsh BT, Ulbrecht J. 2010. Baclofen reduces binge frequency. Appetite 54:641.
Cottone P, Sabino V, Roberto M, Bajo M, Pockros L, Frihauf JB, Fekete
EM, Steardo L, Rice KC, Grigoriadis DE, Conti B, Koob GF, Zorrilla
EP. 2009. CRF system recruitment mediates dark side of compulsive
eating. Proc Natl Acad Sci U S A 106:20016-20020.
Cousins MS, Roberts DC, de Wit H. 2002. GABA(B) receptor agonists for
the treatment of drug addiction: A review of recent findings. Drug Alcohol Depend 65:209-220.
Czyzyk TA, Sahr AE, Statnick MA. 2010. A model of binge-like eating
behavior in mice that does not require food deprivation or stress. Obesity (Silver Spring) 18:1710-1717.
Dagher A. 2009. The neurobiology of appetite: Hunger as addiction. Int J
Obes (Lond) 33 Suppl 2:S30-S33.
Davis C, Carter JC. 2009. Compulsive overeating as an addiction disorder:
A review of theory and evidence. Appetite 53:1-8.
Davis JF, Melhorn SJ, Shurdak JD, Heiman JU, Tschöp MH, Clegg DJ,
Benoit SC. 2007. Comparison of hydrogenated vegetable shortening
and nutritionally complete high-fat diet on limited access-binge behavior in rats. Physiol Behav 92:924-930.
Deroche-Gamonet V, Belin D, Piazza V. 2004. Evidence for addiction-like
behavior in the rat. Science 305:1014-1017.
Dimitriou SG, Rice HB, Corwin RL. 2000. Effects of limited access to a fat
option on food intake and body composition in female rats. Int J Eat
Disord 28:436-445.
Epstein DH, Shaham Y. 2010. Cheesecake-eating rats and the question of
food addiction. Nat Neurosci 13:529-531.
Files FJ, Lewis RC, Samson HH. 1994. Effects of continuous versus limited
access to ethanol on ethanol self-administration. Alcohol 11:523-531.
Gearhardt AN, Corbin WR, Brownell KD. 2009. Preliminary validation of
the Yale Food Addiction Scale. Appetite 52:430-436.
Gearhardt AN, White MA, Potenza MN. 2011. Binge eating disorder and
food addiction. Curr Drug Abuse Rev 4:201-207.
Gendall KA, Joyce PR, Sullivan PF, Bulik CM. 1998. Food cravers: Characteristics of those who binge. Int J Eat Disord 23:353-360.
Goldfein JA, Walsh BT, LaChaussée JL, Kissileff HR, Devlin MJ. 1993.
Eating behavior in binge eating disorder. Int J Eat Disord 14:427-431.
Gosnell BA. 2005. Sucrose intake enhances behavioral sensitization produced by cocaine. Brain Res 1031:194-201.
Guertin TL. 1999. Eating behavior of bulimics, self-identified binge eaters,
and non-eating-disordered individuals: What differentiates these populations? Clin Psychol Rev 19:1-23.
Guss JL, Kissileff HR, Devlin MJ, Zimmerli E, Walsh BT. 2002. Binge size
increases with body mass index in women with binge-eating disorder.
Obes Res 10:1021-1029.
Guthrie JF, Lin BH, Frazao E. 2002. Role of food prepared away from home
in the American diet, 1977-78 versus 1994-96: Changes and consequences. J Nutr Educ Behav 34:140-150.
Volume 53, Number 1
2012
Hagan MM, Shuman ES, Oswald KD, Corcoran KJ, Profitt JH, Blackburn K,
Schwiebert MW, Chandler PC, Birbaum MC. 2002. Incidence of
chaotic eating behaviors in binge-eating disorder: Contributing factors.
Behav Med 28:99-105.
Hagan MM, Wauford PK, Chandler PC, Jarrett LA, Rybak RJ, Blackburn
K. 2002. A new animal model of binge eating: Key synergistic role of
past caloric restriction and stress. Physiol Behav 77:45-54.
Hagan MM, Chandler PC, Wauford PK, Rybak RJ, Oswald KD. 2003. The
role of palatable food and hunger as trigger factors in an animal model
of stress induced binge eating. Int J Eat Disord 34:1831-1897.
Haines J, Gillman MW, Rifas-Shiman S, Field AE, Austin SB. 2010. Family
dinner and disordered eating behaviors in a large cohort of adolescents.
Eat Disord 18:10-24.
Hancock SD, Menard JL, Olmstead MC. 2005. Variations in maternal care
influence vulnerability to stress-induced binge eating in female rats.
Physiol Behav 85:430-439.
Harrington EF, Crowther JH, Henrickson HC, Mickelson KD. 2006. The
relationships among trauma, stress, ethnicity, and binge eating. Cultur
Divers Ethnic Minor Psychol 12:212-229.
Hebb DO. 1949. The Organization of Behavior: A Neuropsychological
Theory. New York: Wiley. p 200-206.
Hetherington MM, MacDiarmid JI. 1993. “Chocolate addiction”: A preliminary study of its description and its relationship to problem eating.
Appetite 21:233-246.
Heyser CJ, Schulteis G, Koob GF. 1997. Increased ethanol self-administration
after a period of imposed ethanol deprivation in rats trained in a limited
access paradigm. Alcohol Clin Exp Res 21:784-791.
Holland PC, Petrovich GD. 2005. A neural systems analysis of the potentiation of feeding by conditioned stimuli. Physiol Behav 86:747-761.
Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. 2007. The prevalence and
correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 61:348-358.
Ifland JR, Preuss HG, Marcus MT, Rourke KM, Taylor WC, Burau K, Jacobs
WS, Kadish W, Manso G. 2009. Refined food addiction: A classic substance use disorder. Med Hypotheses 72:518-526.
Jabs J, Devine CM. 2006. Time scarcity and food choices: An overview.
Appetite 47:196-204.
Johnson PM, Kenny PJ. 2010. Dopamine D2 receptors in addiction-like
reward dysfunction and compulsive eating in obese rats. Nat Neurosci
13:635-641.
Kales EF. 1990. Macronutrient analysis of binge eating in bulimia. Physiol
Behav 48:837-840.
Kinzig KP, Hargrave SL, Honors MA. 2008. Binge-type eating attenuates
corticosterone and hypophagic responses to restraint stress. Physiol Behav 95:108-113.
Koob GF, Le Moal M. 2005. Plasticity of reward neurocircuitry and the
‘dark side’ of drug addiction. Nat Neurosci 8:1442-1444.
Koob GF, Le Moal M. 2006. Animal models of drug addiction. In: Neurobiology of Addiction. San Diego: Academic Press. p 23-67.
Latner JD, Vallance JK, Buckett G. 2008. Health-related quality of life in
women with eating disorders: Association with subjective and objective
binge eating. J Clin Psychol Med Settings 15:148-153.
Liu Y, von Deneen KM, Kobeissy FH, Gold MS. 2010. Food addiction and obesity: Evidence from bench to bedside. J Psychoactive Drugs 42:133-145.
Lo Russo L, Campisi G, Di Fede O, Di Liberto C, Panzarella V, Lo Muzio L.
2008. Oral manifestations of eating disorders: A critical review. Oral
Dis 14:479-484.
Lowe MR, Butryn ML, Didie ER, Annunziato RA, Thomas JG, Crerand
CE, Ochner CN, Coletta MC, Bellace D, Wallaert M, Halford J. 2009.
The Power of Food Scale: A new measure of the psychological influence of the food environment. Appetite 53:114-118.
Marcucella H, Munro I. 1987. Ethanol consumption of free feeding animals
during restricted ethanol access. Alcohol Drug Res 7:405-414.
McGee HM, Amare B, Bennett AL, Duncan-Vaidya EA. 2010. Behavioral
effects of withdrawal from sweetened vegetable shortening in rats.
Brain Res 1350:103-111.
Moreno S, Warren CS, Rodríguez S, Fernández MC, Cepeda-Benito A.
2009. Food cravings discriminate between anorexia and bulimia nervosa:
33
Implications for “success” versus “failure” in dietary restriction. Appetite
52:588-594.
Murphy R, Straebler S, Cooper Z, Fairburn CG. 2010. Cognitive behavioral
therapy for eating disorders. Psychiatr Clin North Am 33:611-627.
Oswald KD, Murdaugh DL, King VL, Boggiano MM. 2011. Motivation for
palatable food despite consequences in an animal model of binge eating.
Int J Eat Disord 44:203-211.
Pankevich DE, Teegarden SL, Hedin AD, Jensen CL, Bale TL. 2010. Caloric restriction experience reprograms stress and orexigenic pathways
and promotes binge eating. J Neurosci 30:16399-16407.
Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF. 2004. Chronic stress
promotes palatable feeding, which reduces signs of stress: Feedforward and
feedback effects of chronic stress. Endocrinology 145:3754-3762.
Pinel JPJ, Huang E. 1976. Effects of periodic withdrawal on ethanol and
saccharin selection in rats. Physiol Behav 16:693-698.
Puhl MD, Cason AM, Corwin RL, Wojnicki FHE, Grigson PS. 2011. A history of bingeing on fat enhances cocaine seeking and taking. Behav
Neurosci 125:930-942.
Rada P, Avena NM, Hoebel BG. 2005. Daily bingeing on sugar repeatedly
releases dopamine in the accumbens shell. Neuroscience 134:737-744.
Raymond NC, Bartholome LT, Lee SS, Peterson RE, Raatz SK. 2007. A
comparison of energy intake and food selection during laboratory binge
eating episodes in obese women with and without a binge eating disorder diagnosis. Int J Eat Disord 40:67-71.
Roberts DC, Morgan D, Liu Y. 2007. How to make a rat addicted to cocaine.
Prog Neuropsychopharmacol Biol Psychiatry 31:1614-1624.
Rogers PJ, Smit HJ. 2000. Food craving and food “addiction”: A critical
review of the evidence from a biopsychosocial perspective. Pharmacol
Biochem Behav 66:3-14.
SAMHSA [Substance Abuse and Mental Health Services Administration].
2010. Results from the 2009 National Survey on Drug Use and Health,
vol I. Summary of National Findings. Office of Applied Studies, NSDUH
Series H-38A, HHS Publication No. SMA 10-4586. Rockville, MD.
Scherag S, Hebebrand J, Hinney A. 2010. Eating disorders: The current
status of molecular genetic research. Eur Child Adolesc Psychiat
19:211-226.
Sisson SB, Broyles ST, Newton RL Jr, Baker BL, Chernausek SD. 2011.
TVs in the bedrooms of children: Does it impact health and behavior?
Prev Med 52:104-108.
Tuomisto T, Hetherington MM, Morris MF, Tuomisto MT, Turjanmaa V,
Lappalainen R. 1999. Psychological and physiological characteristics
of sweet food ”addiction”. Int J Eat Disord 25:169-175.
Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ. 2010. GABA-B receptors in addiction and its treatment. Adv Pharmacol 58:373-396.
34
Vanderschuren LJ, Everitt BJ. 2004. Drug seeking becomes compulsive
after prolonged cocaine self-administration. Science 305:1017-1019.
Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F, Baler R. 2010. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit. Bioessays
32:748-755.
Walsh BT, Kissileff HR, Hadigan CM. 1989. Eating behavior in bulimia.
Ann N Y Acad Sci 575:446-454.
Wang GJ, Volkow ND, Thanos PK, Fowler JS. 2004. Similarity between
obesity and drug addiction as assessed by neurofunctional imaging: A
concept review. J Addict Dis 23:39-53.
Wang GJ, Geliebter A, Volkow ND, Telang FW, Logan J, Jayne MC, Galanti
K, Selig PA, Han H, Zhu W, Wong CT, Fowler JS. 2011. Enhanced
striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring) 19:1601-1608.
Wayner MJ, Fraley S. 1972. Enhancement of the consumption of acclimated sapid solutions following periodic and prolonged withdrawal.
Physiol Behav 9:463-474.
White MA, Grilo CM. 2005. Psychometric properties of the food craving
inventory among obese patients with binge eating disorder. Eat Behav
6:239-245.
Williamson DA, Lawson OD, Bennett SM, Hinz L. 1989. Behavioral treatment of night bingeing and rumination in an adult case of bulimia nervosa. J Behav Ther Exp Psychiat 20:73-77.
Wise RA. 1973. Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacologia 29:203-210.
Wojnicki FH, Roberts DC, Corwin RL. 2006. Effects of baclofen on operant
performance for food pellets and vegetable shortening after a history of
binge-type behavior in non-food deprived rats. Pharmacol Biochem
Behav 84:197-206.
Wojnicki FH, Stine JG, Corwin RL. 2007. Liquid sucrose bingeing in rats
depends on the access schedule, concentration and delivery system.
Physiol Behav 92:566-574.
Wojnicki FH, Charny G, Corwin RL. 2008a. Binge-type behavior in rats
consuming trans-fat-free shortening. Physiol Behav 94:627-629.
Wojnicki FH, Johnson DS, Corwin RL. 2008b. Access conditions affect
binge-type shortening consumption in rats. Physiol Behav 95:649657.
Wojnicki FH, Babbs RK, Corwin RL. 2010. Reinforcing efficacy of fat, as
assessed by progressive ratio responding, depends upon availability not
amount consumed. Physiol Behav 100:316-321.
Yanovski SZ, Leet M, Yanovski JA, Flood M, Gold PW, Kissileff HR,
Walsh BT. 1992. Food selection and intake of obese women with bingeeating disorder. Am J Clin Nutr 56:975-980.
ILAR Journal