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Housing and enrichment conditions are essential factors to consider when using animal models of behavior, as they can alter the behavior that is under investigation. The goal of this study was to determine the impact of the relatively enriched environment recommended by current animal care guidelines on development and maintenance of binge-type behavior in rats, using the limited access (LA) binge model. Non-food-deprived rats were divided into two groups, enriched and nonenriched, with all rats housed in shoebox cages. Bedding, nesting material, toys, and a solid floor were provided only to the enriched group to create a state of relative enrichment, or RE, compared to the nonenriched conditions historically used in the LA model. Enriched and nonenriched groups were further divided into control and experimental groups. Control rats received access to an optional source of fat (vegetable shortening) for 30min each day (daily access) while experimental rats received 30-min optional fat access on Monday, Wednesday, and Friday only (intermittent access). The four groups were designated C-E (Control-Enriched), C-NE (Control-Nonenriched), I-E (Intermittent-Enriched), and I-NE (Intermittent-Nonenriched). Bingeing in the LA model is established when a group with intermittent access (i.e., the I-E or I-NE group) consumes significantly more vegetable shortening during the limited access period than a group with daily access (i.e., the C-E or C-NE group). Access sessions continued for 8weeks under these conditions, at which time the housing conditions of the I-E and I-NE groups were reversed for an additional 8weeks of access sessions. Intakes of the C-E and C-NE groups were similar and data from these two groups were combined. Relative to this Combined Control Group (CCG), the I-NE group began bingeing in week 3 while the I-E group binged during weeks 6 and 8. Following the reversal at the beginning of week 9, the newly enriched I-NE group ceased bingeing in week 9 but resumed bingeing in weeks 10-16. The newly nonenriched I-E group continued bingeing through the remainder of the study. Intakes of the I-E and I-NE groups were not significantly different at any time during the study. These results indicate that RE delays binge onset; that is, RE increases the time between the first fat access session and the first occurrence of bingeing. However, RE does not significantly alter the amount of fat consumed during binge sessions. Furthermore, addition of RE to a nonenriched group of animals (I-NE) does not reverse established binge behavior. Thus it appears that regardless of enrichment condition, intermittent access to vegetable shortening induces greater consumption of fat than does daily access. However, it is clear that a certain level of austerity in housing conditions is required for rapid development of lasting binge-type eating to occur. In addition, results suggest that it is unlikely that enrichment, to the degree provided in this study, can prevent or reverse binge-type eating in rats., (Published by Elsevier Inc.)

Objective: Binge eating is characterized by repeated intermittent bouts of compulsive overconsumption of food. Treatment is challenging given limited understanding of the mechanisms underlying this type of disordered eating. The hypothesis that dysregulation of mesocortical dopaminergic and GABAergic systems underlie binge eating was tested., Methods: Analysis of gene expression within the ventral tegmental area and its terminal mesocortical regions was examined in bingeing rats before and after bingeing occurred. In addition, alterations in binge-type behavior induced by pharmacological inactivation of subnuclei of the prefrontal cortex (PFC) and by pharmacological activation and inhibition of cortical D1 and D2 receptors were examined., Results: Correlative and functional evidence demonstrates dysregulated neurotransmitter processing by the PFC and ventral tegmental area, but not the amygdala or nucleus accumbens, in bingeing rats. Either GABAergic inactivation or D2-like receptor activation within the PFC increased consumption in bingeing rats, but not controls, suggesting that the PFC, and D2 receptors in particular, functions as a behavioral brake to limit bingeing., Conclusions: The act of bingeing resolved some gene expression differences that preceded binge onset, further suggesting that bingeing may partially serve to self-medicate a system driving this maladaptive behavior. However, the failure of bingeing to resolve other dopaminergic/GABAergic differences may render individuals vulnerable to future binge episodes., (© 2016 The Obesity Society.)

Previous studies have shown that providing an optional food for a brief period of time to non-food deprived rats on an intermittent basis in the home cage engenders significantly more intake (binge-type behavior) than when the optional food is provided for a brief period on a daily basis. Experiment 1 examined the effects of placing a small operant response requirement on access to an optional food (vegetable shortening) on the establishment of binge-type behavior. Experiment 2 examined the effects of different schedules of reinforcement, a period of abstinence from shortening, and 24h of food deprivation on established binge-type behavior. In Experiment 1 the group of rats with 30-min access to shortening on an intermittent basis in their home cages (IC) consumed significantly more shortening than the group with 30-min daily access in the home cage (DC). The group with 30-min intermittent access in an operant chamber (IO group) earned significantly more reinforcers than the group with 30-min daily access in an operant chamber (DO). In Experiment 2, the IO group earned significantly more reinforcers than the DO group regardless of the response cost, the period of shortening abstinence, and overnight food deprivation. These results demonstrate that while intermittent access generates binge-type eating, the size of the binge (intake) can be altered by different contingency arrangements., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The GABA-B agonist baclofen has been reported to reduce the consumption of vegetable shortening, but not lard, in rats. This study sought to examine some of the factors that could account for these differences. Baclofen (0, 1.0, 1.8, 3.2 mg/kg, intraperitoneal) was tested: (i) on shortening and lard intake, (ii) under 'binge-type' and non-'binge-type' conditions, (iii) when each fat was presented alone or simultaneously, and (iv) with a 30-min or no pretreatment time. With a 30-min pretreatment time, baclofen (3.2 mg/kg, intraperitoneal) consistently reduced shortening intake under 'binge-type' and non-'binge-type' conditions, as well as when shortening was presented alone or when lard was simultaneously available. Baclofen also reduced lard intake under 'binge-type' and non-'binge-type' conditions, but only when lard was presented alone. Baclofen had no effect on chow intake. When each fat was presented alone, and with no pretreatment time, the results were less consistent; baclofen reduced shortening intake only under non-'binge-type' conditions, and lard intake only under 'binge-type' conditions, and also stimulated chow intake. In summary, the type of fat, the presentation mode (one fat presented alone or two fats simultaneously), and the time between baclofen administration and intake all influence the ability of baclofen to reduce fat intake.

When non-food-deprived rats are given brief access to vegetable shortening (a semi-solid fat used in baked products) on an intermittent basis (Monday, Wednesday, Friday), they consume significantly more and emit more operant responses for shortening than a separate group of rats given brief access to shortening every day. Since both groups are traditionally housed in the same room, it is possible that the environmental cues associated with placing shortening in the cages (e.g., investigator in room, cages opening and closing, etc.) provide predictable cues to the daily group, but unpredictable cues to the intermittent group. The present study examined the effects of providing predictable environmental cues to an isolated intermittent group in order to examine the independent contributions of intermittency and predictability on intake and operant performance. Two groups of rats were housed in the same room, with one group provided 30-min intermittent (INT) access and the second group provided 30-min daily access (D) to shortening. A third group (ISO) of rats was housed in a room by themselves in which all environmental cues associated with intermittent shortening availability were highly predictable. After five weeks of home cage shortening access, all rats were then exposed to several different operant schedules of reinforcement. The INT and ISO groups consumed significantly more shortening in the home cage than the D group. In contrast, the INT group earned significantly more reinforcers than both the ISO and D groups under all but one of the reinforcement schedules, while ISO and D did not differ. These data indicate that intermittent access will generate binge-type eating in the home cage independent of cue predictability. However, predictable cues in the home cage reduce operant responding independent of intermittent access., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Baclofen reduces intake of some foods but stimulates intake or has no effect on others. The reasons for these differences are not known. The present study examined effects of baclofen when composition, energy density, preference, presentation and intake of optional foods varied. Semi-solid fat emulsions and sucrose products were presented for brief periods to non-food-deprived rats. In Experiment 1, fat and sucrose composition were varied while controlling energy density. In Experiment 2A, schedule of access and the number of optional foods were varied. In Experiment 2B, the biopolymer (thickener) was examined. Baclofen reduced intake of fat and/or sugar options with different energy densities (1.28-9kcal/g), when presented daily or intermittently, and when intakes were relatively high or low. However, the efficacy of baclofen was affected by the biopolymer used to thicken the options: baclofen had no effect when options were thickened with one biopolymer (3173), but reduced intake when options were thickened with another biopolymer (515). Baclofen failed to reduce intake of a concentrated sugar option (64% sucrose), regardless of biopolymer. Based upon these results, caution is urged when interpreting results obtained with products using different thickening agents. Systematic research is needed when designing products used in rat models of food intake., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for 4 weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps<0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps<0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p<0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established., (Copyright © 2012 Elsevier Inc. All rights reserved.)

As interest in the study of binge eating has increased, several measures of bingeing have been developed for use in animal models. Two of the measures that have been used to distinguish binge-type from normal intake in animal studies are: (1) comparing intake at a given point in time between groups, and (2) assessing escalation of intake across time within groups. Here we use both of these measures to reanalyze data from 10 previous bingeing experiments conducted in our lab. Additionally, the data from two of these studies were then restructured in order to evaluate the use of these measures in binge eating prone (BEP) and resistant (BER) rats, as described by others. Analyses comparing intake at a given point in time indicated bingeing in all 10 studies, while comparisons of escalation indicated bingeing in 9 out of 10 studies. The goal of this study was to compare and contrast the two measures, identify the strengths and weaknesses of each, and determine their appropriateness for a given set of potential outcomes. The results indicate that both intake and escalation are useful measures. However, their limitations need to be taken into consideration when attempting to operationalize binge-type eating in animal models., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Baclofen has shown promise in treating substance use disorders and also reduced binge frequency in an open-label trial. This placebo-controlled, double-blind, crossover study further assessed the effects of baclofen on binge eating. Twelve individuals who self-reported binge eating completed the study. Data were collected during a run-in period (no drug or placebo), placebo phase (48 days), and baclofen phase (titrated up to 60 mg daily or the maximum tolerated dose, 48 days). All the participants were exposed to all conditions. Participants completed a binge diary daily, and the Binge Eating Scale (BES), Food Craving Inventory-II (FCI-II), and Hospital Anxiety and Depression Scale (HADS) at regular intervals throughout the study. Baclofen significantly reduced binge frequency relative to placebo and run-in (P<0.05). This confirms results from the previous open-label trial. Baclofen also produced slight, but significant, increases in depression symptomatology as assessed by the HADS. Binge severity (BES scores) and craving (FCI-II scores) were significantly reduced during placebo and baclofen phases, that is both measures exhibited significant placebo effects. Tiredness, fatigue, and upset stomach were the most commonly reported side-effects. These results indicate that baclofen may be a useful treatment for binge eating in some patients.

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.

Thickened oil-in-water emulsions are useful model foods in rat studies due to their high acceptance and similarity to foods consumed by humans. Previous work from this laboratory used oil-in-water emulsions thickened with a biopolymer blend containing starch. Intake and effects of baclofen, a GABA-B agonist that decreases fat intake and drug self-administration, were reported, but the contribution of starch was not assessed. In the present study, intake and effects of baclofen were assessed in rats using emulsions prepared with two fat types (32% vegetable shortening, 32% corn oil) and thickened with three biopolymer blends. One biopolymer blend contained starch and the other two did not. Daily 1-h intake of the vegetable shortening emulsion containing starch was significantly greater than the other emulsions. When starch was added to the emulsions originally containing no starch, intake significantly increased. Baclofen generally reduced intake of all emulsions regardless of starch content and stimulated intake of chow. However, effects were more often significant for vegetable shortening emulsions. This report: (1) demonstrates that products used to prepare thickened oil-in-water emulsions have significant effects on rat ingestive behavior, and (2) confirms the ability of baclofen to reduce consumption of fatty foods, while simultaneously stimulating intake of chow., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Binge eating and substance dependence are disorders characterized by a loss of control over consummatory behaviors. Given the common characteristics of these two types of disorders, it is not surprising that the comorbidity between eating disorders and substance abuse disorders is high (20-40%; Conason et al., 2006). It is unknown, however, whether loss of control in one disorder predisposes an individual to loss of control in the other. The present study, therefore, used a rodent model to test whether a history of binge eating would augment subsequent responding for cocaine. Using the limited access protocol described by Corwin et al. (1998), 45 adult male Sprague-Dawley rats were maintained on one of four dietary protocols for a period of six weeks: chow only (Chow; n = 9), continuous access to an optional source of dietary fat (Ad Lib; n = 12), 1-h access to an optional source of dietary fat daily (Daily; n = 12), or 1-h access to an optional source of dietary fat on Monday, Wednesday, and Friday (MWF; n = 12). All four groups also had unrestricted access to a nutritionally complete diet of chow and water. Fat-bingeing behaviors developed in the MWF rats, the group with the most restricted access to the optional fat. Thereafter, cocaine-seeking and -taking behaviors were assessed in all rats using a self-administration protocol modified from that described by Deroche-Gamonet et al. (2004), which focused on the motivation for and preoccupation with obtaining and consuming drug (assessed using a progressive ratio [PR] schedule of reinforcement) and persistence in responding for drug during periods of signaled drug non-availability (SNA). Rats with the MWF history tended to take more cocaine late in fixed ratio (FR) training, they persisted in their efforts to obtain cocaine in the face of signaled non-availability, worked harder for cocaine on a PR schedule of reinforcement, and exhibited more goal-directed behavior toward the cocaine-associated operandum. These results demonstrate a link between binge-type intake of fat and the development of drug-seeking and -taking behaviors, suggesting that a history of fat bingeing may predispose individuals to exhibit more robust "addiction-like" behaviors toward a substance of abuse. Thus, it appears that conditions promoting excessive behavior toward one substance (e.g., a palatable fatty food) beget excessive behavior toward another (e.g., cocaine)., (PsycINFO Database Record (c) 2011 APA, all rights reserved.)

The individual roles of estradiol (E) and progesterone (P) in the control of food intake and body weight in ovariectomized (OVX) rats were investigated. Six groups of OVX Sprague-Dawley rats (n=9/group) were assigned to one of three 4-day cyclic hormone treatments: two groups were treated with E benzoate; two groups were treated with P; two groups were treated with both (EP). All rats had continuous access to chow and water throughout this 4-week study. One group of rats within each hormone treatment condition was fed chow ad libitum, and the second was subjected to a binge schedule: chow ad libitum plus 1-h access to an optional fat source on Monday, Wednesday, and Friday. A seventh OVX group (n=8) received the oil vehicle and chow. This group was included to monitor body weight and to verify hormone efficacy. The main findings were: (1) relative to rats receiving only P, E alone or EP attenuated 24-h chow intake tonically and cyclically, i.e. intake on Day 4, which models estrus, was lower in E and EP than in P, and also was lower than intake on Day 2, which models diestrus. In contrast, (2) neither E nor EP detectably affected optional fat intake during the 1-h fat access period relative to rats receiving only P when data were collapsed across the entire study. However, (3) E and EP had large effects on fat intake relative to P during the 1-h fat access period at the start of the study, but not at the end, when bingeing was fully established. (4) E and EP led to lower and apparently normal levels of body weight compared to rats receiving only the oil vehicle or only P. These results indicate that (1) administration of E alone has similar effects as co-administration of E and P on feeding and body weight in rats bingeing on fat, (2) with or without P, the inhibitory effects of E on meal size are compromised when bingeing on fat, and (3) the effects of E on binge size change dynamically as bingeing develops., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The idea that foods rich in fat and sugar may be addictive has generated much interest, as well as controversy, among both scientific and lay communities. Recent research indicates that fatty and sugary food in-and-of itself is not addictive. Rather, the food and the context in which it is consumed interact to produce an addiction-like state. One of the contexts that appears to be important is the intermittent opportunity to consume foods rich in fat and sugar in environments where food is plentiful. Animal research indicates that, under these conditions, intake of the fatty sugary food escalates across time and binge-type behavior develops. However, the mechanisms that account for the powerful effect of intermittency on ingestive behavior have only begun to be elucidated. In this review, it is proposed that intermittency stimulates appetitive behavior that is associated with uncertainty regarding what, when, and how much of the highly palatable food to consume. Uncertainty may stimulate consumption of optional fatty and sugary treats due to differential firing of midbrain dopamine neurons, activation of the stress axis, and involvement of orexin signaling. In short, uncertainty may produce an aversive state that bingeing on palatable food can alleviate, however temporarily. "Food addiction" may not be "addiction" to food at all; it may be a response to uncertainty within environments of food abundance.

Research has focused on understanding how overeating can affect brain reward mechanisms and subsequent behaviors, both preclinically and in clinical research settings. This work is partly driven by the need to uncover the etiology and possible treatments for the ongoing obesity epidemic. However, overeating, or non-homeostatic feeding behavior, can occur independent of obesity. Isolating the variable of overeating from the consequence of increased body weight is of great utility, as it is well known that increased body weight or obesity can impart its own deleterious effects on physiology, neural processes, and behavior. In this review, we present data from three selected animal models of normal-weight non-homeostatic feeding behavior that have been significantly influenced by Bart Hoebel's 40+-yr career studying motivation, feeding, reinforcement, and the neural mechanisms that participate in the regulation of these processes. First, a model of sugar bingeing is described (Avena/Hoebel), in which animals with repeated, intermittent access to a sugar solution develop behaviors and brain changes that are similar to the effects of some drugs of abuse, serving as the first animal model of food addiction. Second, another model is described (Boggiano) in which a history of dieting and stress can perpetuate further binge eating of palatable and non-palatable food. In addition, a model (Boggiano) is described that allows animals to be classified as having a binge-prone vs. binge-resistant behavioral profile. Lastly, a limited access model is described (Corwin) in which non-food deprived rats with sporadic limited access to a high-fat food develop binge-type behaviors. These models are considered within the context of their effects on brain reward systems, including dopamine, the opioids, cholinergic systems, serotonin, and GABA. Collectively, the data derived from the use of these models clearly show that behavioral and neuronal consequences of bingeing on a palatable food, even when at a normal body weight, are different from those that result from simply consuming the palatable food in a non-binge manner. These findings may be important in understanding how overeating can influence behavior and brain chemistry., (Copyright © 2011 Elsevier Inc. All rights reserved.)

One conundrum of binge eating is that women are more likely to suffer from binge-related disorders, even though estradiol decreases food intake. 2-hydroxyestradiol (2OHE2), an estrogen metabolite, may account for the contradiction, due to possible interference with DA signaling. We hypothesized that 2OHE2 would enhance bingeing in a rodent model. Two cohorts (1 male, 1 female) of 34 non-food-deprived rats were separated into daily control (D) (received an optional source of dietary fat for 20 min every day) or bingeing (INT) groups (received fat intermittently, i.e. 20 min on Mon, Weds, Fri). During the 5-week binge induction period, shortening intakes escalated significantly faster in females than in males, such that males consumed significantly less fat/kg body mass than did females after 5 weeks. This result is consistent with the idea that biological differences contribute to sex differences in bingeing. Rats were then injected with 2OHE2 (1.0, 3.0, and 10.0 μg/kg intraperitoneally), vehicle, or 2-methoxyestradiol (2ME2) immediately prior to fat access. Fat intake was significantly stimulated by 2OHE2 only in the INT rats (p<0.03). Furthermore, this effect seemed to be more subtle in females than in males. Thus, 2OHE2 appears to exacerbate binge size. These data suggest a novel biological mechanism for sex differences in the risk of eating disorders., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Intermittent limited access to an optional source of dietary fat can induce binge-type behavior in rats. However, the ability of such access to alter the reinforcing efficacy of fat has not been clearly demonstrated. In this study, performance under progressive ratio one (PR1) and three (PR3) schedules of shortening (fat) reinforcement was assessed in non-food deprived rats (n=15/group). One group of rats had intermittent access to a dietary fat option (INT, 1-hour shortening access in the home cage each Monday, Wednesday, and Friday), whereas the other group had daily access to the fat option (D, 1-hour shortening access daily). Chow and water were continuously available. After five weeks, the INT group consumed more shortening during the 1-hour access period than did the D group. Rats were then trained to lever press for a solid shortening reinforcer (0.1 gm). INT rats earned significantly more reinforcers than did D rats under PR1, but not under PR3. Subgroups of INT and D rats (n=7 each) were matched on the amount of shortening consumed in the home cage during week five of the protocol and the PR data were reanalyzed. The INT subgroup earned significantly more reinforcers than the D subgroup did under PR1, but not PR3. These results demonstrate that: (1) intermittent access to shortening in the home cage, but not the amount consumed during the access period (i.e. bingeing), increases the reinforcing efficacy of solid shortening; and (2) the type of PR schedule is critical in delineating differences between the groups., ((c) 2010 Elsevier Inc. All rights reserved.)

Gamma-aminobutyric acid (GABA), dopamine, and opioids are implicated in impulse control, addiction and binge eating. Recent evidence suggests that sucrose alters the effects of GABAergic, dopaminergic, and opioid receptor ligands on consumption of a fatty food in a rat limited-access binge protocol. This study determined the independent effects of fat and sucrose on the efficacy of these ligands under limited-access conditions. Nonfood-deprived male Sprague-Dawley rats had 1 h access to fat (vegetable shortening) or sucrose (3.2, 10, or 32% w/v). Half had intermittent access (Monday, Wednesday, Friday) and half had daily access. Effects of baclofen (GABAB agonist), SCH 23390 (D1 antagonist), raclopride (D2 antagonist), and naltrexone (opioid antagonist) were assessed. Baclofen and naltrexone reduced fat intake regardless of the access schedule. Baclofen had no effect on sucrose intake; naltrexone reduced sucrose intake at higher doses than were required to reduce fat intake. Raclopride stimulated fat intake in intermittent-access rats and had no effect in daily-access rats; raclopride reduced sucrose intake in all groups. SCH 23390 reduced intake in a nonspecific manner. The results indicate the involvement of GABAB receptors in fat but not sucrose intake, and of D2 receptor dysfunction in rats with a history of bingeing on fat.

This study assessed the effects of the opioid antagonist naltrexone, the dopamine 2-like (D2) antagonist raclopride, and the GABA(B) agonist baclofen on consumption of fat/sucrose mixtures (FSM) using a limited access protocol. Sixty male Sprague-Dawley rats were grouped according to two schedules of access (Daily [D] or Intermittent [I]) to an optional FSM. Each FSM was created by whipping 3.2% (L), 10% (M), or 32% (H) powdered sugar into 100% vegetable shortening in a w/w manner (n=10 per group). One-hour intakes of the IL and IM groups were significantly greater than intakes of the respective DL and DM groups, thus fulfilling our operational definition of binge-type eating in these groups. Baclofen reduced intakes of the L and M mixtures regardless of access schedule, but failed to reduce intake of the H mixture. Naltrexone reduced intake in all groups, but potency was greater in IL rats than in DL rats. Furthermore, potency was attenuated in Intermittent rats, but enhanced in Daily rats, at higher sucrose concentrations. Raclopride reduced intake in the DL and stimulated intake in the IL groups, reduced intake in both M groups, and was without effect in both H groups. These results indicate that fat/sucrose mixtures containing relatively low concentrations of sucrose allow distinctions to be made between: 1) intakes stimulated by different access schedules and 2) opioid and dopaminergic modulation of those intakes. These results also suggest that brief bouts of food consumption involving fatty, sugar-rich foods may prove to be particularly resistant to pharmacological intervention.

Food addiction is a pervasive, yet controversial, topic that has gained recent attention in both lay media and the scientific literature. The goal of this series of articles is to use a combination of preclinical and clinical data to determine whether foods, like drugs of abuse, can be addictive, the conditions under which the addiction develops, and the underlying neurophysiological substrates. Operational definitions of addiction that have been used in the treatment of human disorders and to guide research in both humans and animals are presented, and an overview of the symposium articles is provided. We propose that specific foods, especially those that are rich in fat and/or sugar, are capable of promoting "addiction"-like behavior and neuronal change under certain conditions. That is, these foods, although highly palatable, are not addictive per se but become so following a restriction/binge pattern of consumption. Such consummatory patterns have been associated with increased risk for comorbid conditions such as obesity, early weight gain, depression, anxiety, and substance abuse as well as with relapse and treatment challenges. The topic of food addiction bears study, therefore, to develop fresh approaches to clinical intervention and to advance our understanding of basic mechanisms involved in loss of control.

When non-food-deprived rats are given intermittent access to certain substances, consumption of those substances is greater than when more frequent access is provided. The present study examined the effects of three different shortening access conditions on subsequent shortening intake in rats. Each of the three different shortening conditions lasted five weeks and was followed by a five-week period in which shortening access was limited by time (1 h of availability) on either an Intermittent (Monday, Wednesday, Friday) or Daily schedule of access. In Part 1, limiting the quantity of shortening provided during the 1-h period of availability attenuated subsequent 1-h shortening intake in the Intermittent access group, but had no statistically significant effect in the Daily access group. In Part 2, unrestricted availability of shortening (24 h/day-7 days/week) attenuated subsequent 1-h shortening intake in all groups. In Part 3, shortening non-availability for five weeks enhanced subsequent 1-h shortening intake in all groups. It was also shown that rats under an Intermittent, but not a Daily, schedule of access consumed as much shortening during a 1-h period of availability, as was consumed in 24 h when shortening availability was unrestricted. These results demonstrate that while intermittent access is necessary and sufficient to stimulate binge-type eating in rats, the behavioral history can modulate binge size.

Binge eating is more common in females than in males. This study investigated the effects of ovarian hormones on binge-eating behavior in a diet-related rat model. Six groups of ovariectomized Sprague-Dawley rats were used (n=13/group). All rats had continuous access to chow and water throughout the study. One half of the rats were injected every fourth day with estradiol benzoate (2 microg/100 microl sesame oil) and progesterone (500 microg/100 microl sesame oil); the other half received only the sesame oil vehicle. Three feeding protocols were tested in each hormone injection condition: (1) chow only: no additional dietary fat access; (2) low-restriction: 1-h fat access every day; (3) high-restriction: 1-h fat access on Monday, Wednesday, and Friday. As previously reported in intact male and female rats, the high-restriction groups exhibited binge-like increases in 1-h energy intake during fat access. The major new finding of this study is that 1-h energy intake was tonically, but not cyclically, reduced in the hormone-treated high-restriction (binge) rats. Specifically, both low- and high-restriction hormone-treated rats consumed significantly less energy than did the oil-treated rats during the 1-h fat period (p<0.0001) and overall (p<0.0001), indicating a tonic inhibition of eating. However, food intake during the 1-h fat access period was also cyclically reduced in the hormone-treated low-restriction rats, but not in the hormone-treated high-restriction rats. These results indicate that the normal cyclic inhibitory influence of ovarian hormones on eating, but not their normal tonic inhibitory influence, is disrupted by conditions leading to binge-type eating.

Studies from this and another laboratory involving an animal model of binge-type behavior have used vegetable shortening containing trans-fats. Due to reformulations by vegetable shortening manufacturers to remove trans-fats from their products, only trans-fat-free shortenings are now available. The goal of the present study was to assess binge-type behavior in rats with trans-fat and trans-free vegetable shortening. Trans-fat-free shortening was provided to three different groups of non-food-deprived male Sprague Dawley rats on different schedules of access: continuous access (24 h/day-7 days/week), daily access (1 h every day), and intermittent access (1 h on Mondays, Wednesdays, Fridays). Trans-fat shortening was provided to a fourth group on the intermittent access schedule. A fifth group had no shortening access (chow only). Both intermittent groups (trans-fat-free and trans-fat) consumed significantly more shortening during the 1-h period of availability than did the daily group, and there was no difference in shortening intakes between the intermittent groups. These results are identical to previous reports of binge-type behavior in rats using this model. Thus, binge-type behavior in the present behavioral model depends upon the schedule of access, not the presence of trans-fats in the shortening.

Previous work in rats has demonstrated that an Intermittent (Monday, Wednesday, Friday) schedule of access promotes binge-type consumption of 100% vegetable shortening during a 1-h period of availability. The present study used novel shortening-derived stable solid emulsions of various fat concentrations. These emulsions were the consistency of pudding and did not demonstrate oil and water phase separation previously reported with oil-based liquid emulsions. Male Sprague-Dawley rats were grouped according to schedule of access (Daily or Intermittent) to one of three concentrations (18%, 32%, 56%) of solid fat emulsion. There were no significant Intermittent vs. Daily differences in amount consumed, due to high intakes in all groups. This indicated the acceptability of the emulsions. Baclofen (GABA(B) agonist) and raclopride (D2-like antagonist) both significantly reduced emulsion intake in all Daily groups, but only in the 56% fat Intermittent group. Naltrexone (opioid antagonist), in contrast, significantly reduced 32% and 56% fat emulsion intake in the Intermittent, as well as the Daily groups. These results indicate that the fat intake-reducing effects of GABA(B) activation and D(2) blockade depend upon fat concentration and schedule of fat access, while the fat intake-reducing effects of opioid blockade depend upon fat concentration but not schedule of access.

Objective: Baclofen is a GABA-B agonist that may be useful in the treatment of substance use disorders, and also reduces 'binge-like' eating in rodents. We hypothesized that baclofen might be effective in reducing binge eating episodes in binge eating disorder (BED) and bulimia nervosa (BN)., Method: Seven women with BED (n = 4) or BN (n = 3) took baclofen (60 mg/day) for 10 weeks., Results: Six out of seven patients completed the full 10-week trial. Five out of seven participants (3 BED; 2 BN) demonstrated 50% or greater reduction of frequency of binge eating from beginning to end of the study. Three out of seven participants (2 BED; 1 BN) were free of binge eating at study end. Four out of seven participants elected to continue baclofen at study end. Baclofen was well tolerated by the participants., Conclusion: In this open-label trial, baclofen was associated with decreased binge eating frequency in patients with BED and BN., ((c) 2007 by Wiley Periodicals, Inc.)

Previous studies have reported binge-type consumption of solid vegetable shortening in non-food deprived rats maintained on schedules of limited shortening access. The current study determined if limited access would promote binge-type consumption of sucrose solutions. Adult male rats (6 groups, n = 10 each) were provided with one of three different sucrose concentrations (3.2%, 10%, 32% w/v) for 2 h either everyday (Daily) or Monday, Wednesday, and Friday (Intermittent). A 'binge' during the 2-h access periods was operationally defined as Intermittent intakes significantly greater than Daily intakes. Sucrose initially was provided in a 100 ml glass tube equipped with a stainless-steel drinking spout. Under these conditions, there were no differences in sucrose intake between Daily and Intermittent groups at any of the concentrations. In contrast, when sucrose was provided in a modified 60 ml plastic syringe with the same drinking spout, intakes of the Intermittent groups consuming 3.2% and 10% sucrose were greater than those of the respective Daily groups, indicating that binge-type consumption of sucrose occurred. These results demonstrate that brief, intermittent access to low and moderate concentrations of sucrose can promote binge-type behavior, and the characteristics of the drinking apparatus can affect sucrose intake.

Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n = 23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 +/- 1.21 nM BCE), relative to the AAD (15.59 +/- 1.21 nM BCE) (p < 0.05). Mean NTx level following the LA diet was 13.80 +/- 1.21 nM BCE. There was no change in levels of BSAP across the three diets. Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFalpha for all three diets. The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation.

In this protocol, binge-type eating is induced in non-food-deprived rats by providing limited access to an optional source of dietary fat: vegetable shortening. The protocol is simple and inexpensive, and the binge behavior is robust, reliable, and maintainable across extended periods of time. Two peptides that normally affect fat intake in rats have no effect on fat intake under limited-access conditions. However, recent results with a GABA(B) receptor agonist and with progressive-ratio responding suggest that the behavior induced by the limited-access binge protocol may share similarities with substance abuse. This protocol is designed to model the kind of excessive behavior that characterizes bingeing-related eating disorders and certain addictions.

Operant performance of non-food deprived rats (n=8) was assessed under progressive ratio (PR) and concurrent PR-fixed ratio schedules of food pellet and/or vegetable shortening reinforcement. Post operant baselines, rats were matched and divided into 2 groups based upon the schedule of shortening availability: High restriction binge group (H, 1-hr home cage shortening access each week on Monday, Wednesday, and Friday) and Low restriction (L, 1-hr shortening access daily). Chow and water were continuously available; only access to the shortening was restricted. After 8 weeks, operant performance was reassessed. Lever pressing for shortening increased in the H rats for all schedules, but was either unaffected or decreased in the L rats. Pellet responding under the concurrent schedules increased for both groups. The effects of four dosages of (R)-baclofen (0.3-1.8 mg/kg, i.p.) on operant performance were also assessed. For both groups, 1.0 mg/kg baclofen significantly reduced shortening responding relative to saline for all schedules except one, but had no or minimal effect on pellet responding. This suggests a specific effect of baclofen on responding maintained by fat. These results indicate that intermittent episodes of bingeing on fat can increase the reinforcing efficacy of fat and that GABAB receptor activation can attenuate this effect.

Intermittent excessive behaviors (IEB) characterize a variety human disorders including binge eating, drug abuse, alcoholism, aberrant sexual conduct, and compulsive gambling. Clinical co-morbidity exists among IEB, and limited treatment options are available. The use of behavioral models of bingeing and other feeding protocols is beginning to clarify neural similarities and differences that exist between IEB directed toward obtaining and consuming food and IEB directed toward obtaining and consuming drugs of abuse. Research from this laboratory using a limited access binge-type eating protocol may provide new insight into IEB.

Mounting evidence indicates that the amount and type of fat in the diet can have important effects on bone health. Most of this evidence is derived from animal studies. Of the few human studies that have been conducted, relatively small numbers of subjects and/or primarily female subjects were included. The present study assessed the relation of dietary fat to hip bone mineral density (BMD) in men and women using NHANES III data (n = 14,850). Multivariate models using SAS-callable SUDAAN were used to adjust for the sampling scheme. Models were adjusted for age, sex, weight, height, race, total energy and calcium intakes, smoking, and weight-bearing exercise. Data from women were further adjusted for use of hormone replacement therapy. Including dietary protein, vitamin C, and beta-carotene in the model did not influence the outcome. Analysis of covariance was used to generate mean BMD by quintile of total and saturated fat intake for 4 sex/age groups. Saturated fat intake was negatively associated with BMD at several hip sites. The greatest effects were seen among men < 50 y old (linear trend P = 0.004 for the femoral neck). For the femoral neck, adjusted mean BMD was 4.3% less among men with the highest compared with the lowest quintile of saturated fat intake (BMD, 95% CI: highest quintile: 0.922 g/cm2, 0.909-0.935; lowest quintile: 0.963 g/cm2, 95% CI: 0.950-0.976). These data indicate that BMD is negatively associated with saturated fat intake, and that men may be particularly vulnerable to these effects.

In this paper, a framework involving four aspects to be considered when establishing an operational definition of non-homeostatic appetitive behavior is presented. The four aspects are (1) the quantity of the commodity consumed, (2) the quality or type of commodity consumed, (3) the context in which the behavior occurs, and (4) the specific kind of behavior that is directed toward obtaining and consuming the commodity of interest. This framework permits comparisons among a variety of non-homeostatic behaviors and accommodates different theoretical approaches reflected in the use of mechanistic, systems, behavioral, nutritional, and clinical experimental strategies. The speakers of this symposium were selected to emphasize the four aspects of non-homeostatic behavior, to represent several different approaches, and to facilitate discussion regarding neural similarities and differences between non-homeostatic eating and drug abuse. The various talks illustrated that boundaries need not exist among research fields, and that communication among the various areas enhances the research effort.

The GABA-B agonist baclofen reduces drug self-administration in rats and has shown promise clinically in the treatment of substance abuse. Baclofen generally does not reduce food intake in non-binge feeding protocols. In this study, baclofen was tested in a fat-binge protocol. Thirty male rats were divided into three groups (B: binge; FM: fat-matched; C: chow). B received a bowl of vegetable shortening for 2 h on Monday, Wednesday, and Friday (MWF) and continuous access to powdered chow (regular chow) in all phases. FM had continuous access to a regular chow+shortening mixture (FM chow) that provided the same proportion of shortening and regular chow that the B rats consumed in all phases. In addition, FM had the following: phase 1: no separate bowl of shortening; phase 2: 2-h MWF access to a separate bowl of shortening; phase 3, daily 2-h access to a separate bowl of shortening; C rats had continuous access to the regular chow in all phases. In addition, C had the following: phase 1: no separate bowl of shortening; phase 2: 2-h MWF access to a separate bowl of shortening; in phase 3, daily 2-h access to a separate bowl of shortening. Baclofen (1.0, 1.8 mg/kg, i.p.) reduced shortening intake regardless of access condition. Baclofen had no effect on, or stimulated, FM and regular chow intake. These results demonstrate that baclofen can reduce fat intake in rats under binge-type conditions. Furthermore, these results indicate that bingeing, as modeled in our protocol, is different from other forms of food intake and may share similarities with substance abuse.

Purpose: To describe and evaluate behavioral models of binge-type eating., Data Identification: Studies were identified using Medline and hand searches of bibliographies of identified articles., Study Selection: Isomorphic studies were selected that were judged to have some measure of construct validity., Data Extraction: Face and construct validity were assessed, as well as simplicity and cost of use., Results of Data Synthesis: Several different models of binge-type eating exist, each with different strengths of validity and use. These include models using sham feeding, restriction/refeeding cycles and/or stress, limited access (LA) to optional foods, and eating induced by operant schedules of behavior., Conclusions: We concur with Harry Harlow, who was quoted by Gerry Smith as saying: "You'd be crazy to use animal models, but you'd also be crazy not to use them."

This study was designed to determine if a limited access feeding protocol would induce binge-type eating when energy intake on the day before the binge was not reduced. Rats were assigned to four groups; all groups had continuous access to chow and water throughout the 4 wk study. In addition, access to optional shortening was provided as follows: (1) Control (C): no access to shortening, (2) Regular Shortening Access-7 (RSA7): 2-h access everyday, (3) Regular Shortening Access-3 (RSA3): 2-h access every Monday, Wednesday, and Friday, (4) Irregular Shortening Access (ISA): 2-h access on various days, such that the number of shortening access (binge) sessions equaled that of RSA3, but the last three sessions were each separated by 4 days. On the days prior to the last two binge sessions, RSA3 consumed significantly less energy than any other group (p < 0.05) but ISA intakes equaled those of Control and RSA7. During the last two binge sessions, intakes of RSA3 and ISA did not differ, and both groups consumed significantly more than RSA7 or Control (p < 0.05) These results demonstrate that binge-type eating can be induced by limiting access to an optional fatty food, and does not depend upon undereating on the previous day.

Evidence is accumulating that dietary lipids play an important role in bone health. Most of the data supporting the effects of lipids on bones have been collected in young adult and/or developing animals. Based upon this work, mechanisms have been proposed to explain how lipids act to enhance or inhibit bone resorption and deposition. Little work, however, has been done in older models. Since osteoporosis primarily afflicts the elderly, such work is needed in order to determine if mechanisms relevant to the young differ in advanced age, and to develop effective interventions for this especially vulnerable segment of the population. This article reviews evidence that dietary lipids are important to bone health in older individuals, and describes possible mechanisms that may be of particular relevance to the elderly. Specifically, studies supporting the influence of dietary lipids on calcium excretion, growth hormone secretion, fatty acid metabolism, and osteoblast formation are reviewed.

The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to modify central serotonergic parameters relevant to ingestive behavior. Evidence suggests an association between the 5-HT(2C) receptor and fat intake. The present research sought to examine the role of the 5-HT(2C) receptor subtype on food intake when diets with different fatty acid compositions are consumed. The effects of 1-(3-chlorophenyl)piperazine (mCPP) on consumption of both low-fat (Experiment 1) and high-fat diets (Experiment 2) differing in their predominant PUFA profiles were compared in rats. Regardless of the PUFA profile, mCPP induced hypophagia within each experiment. Although the present results lend further support to a large body of evidence demonstrating the ability of mCPP to reduce food intake, they do not support the idea that the essential fatty acid composition of the diet can differentially modulate mCPP-induced hypophagia.

Alterations in the ability to adjust energy intake when optional dietary foods are available may contribute to aging-related changes in body composition. Ingestive behavior, however, has not been extensively studied in aging models. The present research used young, middle-aged and old rats to examine food intake under several different schedules of optional fat availability. All rats were provided with continuous access to a nutritionally complete diet throughout the 6-week study. In addition, different subgroups within each age had access to an optional source of vegetable shortening under schedules in which the frequency of access was manipulated: controls (C)-- no shortening access; MWF--2-h shortening access on Monday, Wednesday and Friday; D2--2-h shortening access every day; D24--24-h shortening access every day. Energy intake was significantly greater in groups with more frequent access to shortening regardless of age. The length of time the rats remained hyperphagic, however, increased with age. Body weight increased significantly in the D24 group in middle-aged and old rats, but not in young rats. Total body fat was also significantly higher in middle-aged and old groups with more frequent access to shortening, but not in young rats. Finally, body ash mass was significantly reduced in old rats on the D24 diet. These results suggest that alterations in responses to an optional source of dietary fat may contribute to aging-associated body fat accretion and body mineral loss.

Food intake may be differentially responsive to the type of fat in the diet. The present investigation sought to evaluate the energy intake of rats maintained on either a low-fat or a high-fat diet mixed with an oil rich in either linoleic (18:2; n-6; safflower oil) or linolenic (18:3; n-3; flaxseed oil) acid. In Experiment 1, rats (n=28) consumed low-fat versions of either the safflower oil diet or the flaxseed oil diet, each at 9.28% fat (wt/wt). In Experiment 2, different rats (n=28) consumed high-fat versions of these diets, each at 23.6% fat (wt/wt). Within each experiment, the energy intake of rats receiving the safflower oil diet was compared to the energy intake of rats receiving the flaxseed oil diet. Food intake was measured under short-term, long-term and food-deprived conditions. In Experiment 1, short-term energy intakes were not different between the groups, thus demonstrating equal acceptance of the test diets. There were no consistent differences in long-term energy intakes between the safflower group and the flaxseed group. In addition, there were no differences in energy intake under the food-deprivation condition. Results from Experiment 2 paralleled those of Experiment 1. Taken together, the present results suggest that the essential fatty acid profile of the maintenance diet does not influence food intake when nutritive oils are the predominant fatty acid source.

Objective: The present investigation sought to determine if limiting access to an optional fatty food would induce binge-type behavior patterns in non-energy-deprived female rats., Method: Four groups of rats had continuous access to a commercial rodent diet throughout the 8-week study. In addition: (1) the control group had no access to vegetable shortening; (2) the high limitation group had access to shortening for 2 hr for 3 days each week; (3) the low limitation group had access to shortening for 2 hr every day; and (4) the no limitation group had continuous access to shortening., Results: As access to the shortening decreased, intake during the 2-hr access period increased. Total energy intake and body weight did not differ among groups. Body fat was greatest in the rats that ate the most cumulative shortening., Discussion: These results indicate that, even under non-energy-deprived conditions, limiting access to a preferred fatty food can induce binge-type behavior in female rats., (Copyright 2000 by John Wiley & Sons, Inc.)

While preference for fat can be influenced by concentration and physical form, the influence of fatty acid composition on relative preference for oils has not been systematically investigated. Therefore, the purpose of the present investigation was to assess the relative preference for oils rich in oleic (Extra Light Olive Oil and Extra Virgin Olive Oil) and linoleic (Safflower Oil) acid. Male Fischer rats (n = 10) were used to determine preference in a two-choice testing procedure in which three pairs of oils were each tested twice. Preference testing occurred at dark onset at which time the rodent diet and water were removed and each rat was allowed 2-h access to his assigned pair of oils. There was a main effect of oil type (p<0.01), but no significant effect of oil pairing and no interaction between oil pairing and oil type. Rats preferred the Extra Light Olive Oil to the Extra Virgin Olive Oil (p<0.05). This is the first report of preference testing in which two oils with similar fatty acid profiles were included. The present data indicate that the fats with similar fatty acid profiles were not equally preferred, suggesting that a property other than the fatty acid composition of the oils accounts for the demonstrated preference.

Restricting access to high-fat foods is a common strategy utilized to promote health. This strategy may contribute to episodes of overconsumption, however, when the restricted foods subsequently become available. The present study utilized a rat feeding procedure to determine if restricting access to an optional source of dietary fat would increase later consumption of that food under nonenergy-deprived conditions. Five groups of male Sprague-Dawley rats were used, all of which had continuous access to a standard rodent diet and water. The control group had no access to shortening. The low-restriction group had 2-h access to shortening every day. The high-restriction group had 2-h access to shortening on Monday, Wednesday, and Friday. Two additional groups were switched between the high and low conditions. Two-hour and 24-h food intakes were measured every day for 6 weeks. At the end of the study rats were sacrificed and carcass composition determined. As access to the shortening decreased, consumption during the 2-h access period increased. Rats compensated for the increased shortening consumption by decreasing intake of the standard diet. Thus, cumulative energy consumption did not differ among the groups. When switched between the high and low conditions, rats rapidly adjusted to the change in shortening availability. There were no effects of access schedule on carcass composition. These results indicate that restricting access to an optional high-fat food, even under nonenergy-deprived conditions, can promote significant increases in the consumption of that food when it subsequently becomes available.

The peptide enterostatin has been proposed to function as a selective signal for fat-induced satiety. In the majority of enterostatin studies, however, rats were food-deprived, and the test food was also the maintenance diet. The present study sought to determine if enterostatin would selectively reduce consumption of oil that was provided in addition to a standard diet in non-food-deprived rats. Rats had either continuous (24-h/day) or limited access (120-min/day) to either a 32% sucrose solution or 100% corn oil. In addition to the sucrose and the oil, rats also had 22-h access to a standard pelleted rodent diet. Control rats had unlimited access to the standard diet but no access to oil or sucrose. Rats were maintained on their respective diets for 3 weeks before enterostatin testing. Food intake and body weight were monitored. Rats with continuous access to oil or sucrose consumed more calories and gained more weight than control rats. Caloric intake and body weight of the rats with limited access to oil or sucrose did not differ significantly from controls. Enterostatin, administered intraperitoneally (i.p.) at doses of 0 (vehicle), 89, 178, and 356 microg/kg, had no effect on consumption of oil, sucrose, or standard diet in these non-food-deprivation paradigms; however, 356 microg/kg reduced standard-diet intake when rats were overnight food-deprived, thus verifying peptide activity. These results do not support a role for enterostatin in the regulation of fat intake when optional high-fat foods are provided in addition to a readily available standard diet.

Enterostatin, the activation peptide of procolipase, has been reported to reduce high-fat food consumption in rats. This reduction has been reliably demonstrated using procedures in which the test diet was also the maintenance diet of the animals. Other reports, though, have shown that peripherally administered enterostatin had no effect on the consumption of oil provided as an option to the diet, and that centrally administered enterostatin had no effect on the consumption of an optional high-fat mixed food. However, the effects of peripherally administered enterostatin on the consumption of an optional high-fat mixed food have not been examined. This experiment, then, examined the effects of peripherally administered enterostatin on the consumption of optional, mixed foods (no-fat and high-fat cookies) provided in addition to a standard diet under choice and nonchoice conditions. Four experiments were conducted. In experiment I, the effect of enterostatin in a two-choice feeding paradigm was assessed. In experiment II, the effect of enterostatin in a nonchoice feeding paradigm was assessed. In experiment III, the effect of enterostatin administered at five different pretreatment times in a non-choice feeding paradigm was assessed. Enterostatin had no effect on cookie intake in any of these experiments. Finally, experiment IV was undertaken to verify the activity of the peptide. Enterostatin significantly reduced the consumption of a standard diet in overnight food-deprived rats, thus confirming the activity of the peptide used in experiments I to III. Enterostatin may not play a major role in the regulation of food intake that is stimulated by optional foods that are periodically provided in addition to a standard well-balanced diet.

Previous studies reported that ICV enterostatin reduced high-fat food intake in food-deprived rats. The present study sought to determine if ICV enterostatin would decrease intake of a high-fat food in non-food-deprived rats. Eight doses (0-32 micrograms) were tested. Enterostatin (32 micrograms) significantly stimulated cookie intake at 30 min. Enterostatin did not reduce food intake at any dose. These results conflict with previous reports and suggest that central enterostatin does not play a role in suppressing, but may play a role in stimulating, high-fat food consumption in non-food-deprived rats.

The neuropeptide galanin has been proposed to play a role in the regulation of fat intake. The purpose of the present investigation was to determine if galanin and the galanin receptor antagonist M40 would have selective effects on fat intake in a fat-chow choice paradigm in rats. Rats were adapted to 22-h access to chow alone and 2-h daily access to separate sources of fat and chow in the early dark cycle. Galanin (300 pmol, 1 nmol) or M40 (2-500 pmol) was microinjected bilaterally into the paraventricular nucleus of the hypothalamus (PVN) before the 2-h choice period, and chow and fat intake were measured. M40 had no effect on chow or fat intake. Galanin stimulated chow intake and increased the ratio of chow to fat consumed but had no significant effect on fat intake alone. These results suggest that endogenous galanin in the PVN may not play a primary role in the regulation of fat intake when fat is available in addition to a nutritionally balanced diet.

CI-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI-988 perfusion and returned to baseline levels upon cessation of CI-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of CI-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular.

Cholecystokinin (CCK) has emerged as an important mammalian neuropeptide, localized in peripheral organs and in the central nervous system. This review presents an overview of the molecular aspects of CCK peptides and CCK receptors, the anatomical distribution of CCK, the neurophysiological actions of CCK, release of CCK and effects of CCK on release of other neurotransmitters, and the actions of CCK on digestion, feeding, cardiovascular function, respiratory function, neurotoxicity and seizures, cancer cell proliferation, analgesia, sleep, sexual and reproductive behaviors, memory, anxiety, and dopamine-mediated exploratory and rewarded behaviors. Human clinical studies of CCK in feeding disorders and panic disorders are described. New findings are presented on potent, nonpeptide CCK antagonists, selective for the two CCK receptor subtypes, which demonstrate that endogenous CCK has biologically important effects on physiology and behavior.

Anandamide (arachidonylethanolamide), an arachidonic acid derivative isolated from the porcine brain, displays binding characteristics indicative of an endogenous ligand for the cannabinoid receptor. The functional activity of anandamide was tested in vivo using behavioral and physiological paradigms in laboratory rodents. At IP doses from 2 to 20 mg/kg in mice, anandamide significantly decreased spontaneous motor activity in a Digiscan open field. Rectal body temperature significantly decreased at doses of 10 and 20 mg/kg in rats. At doses from 0.03 to 30 mg/kg, anandamide had no significant effect on chow consumption in ad lib fed rats. Over the dose range of 2-20 mg/kg, anandamide did not show anxiolytic properties in the mouse light<-->dark exploration model of anxiety. Over the dose range of 0.3-3 mg/kg, anandamide had no effect on choice accuracy or session duration in the delayed nonmatching to sample memory task (DNMTS) in rats. These results demonstrate that anandamide has biological and behavioral effects in awake rodents, some of which are similar to the reported actions of THC.