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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.

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.)

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.)

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.)

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.

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.

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.

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.

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.

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.

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.

To assess the role of cholecystokinin (CCK) receptors in mediating the satiating effect of an oral preload, overnight food-deprived rats (n = 7) were given access to a high-carbohydrate liquid diet for 40 min. At the end of 40 min, food was removed and rats were injected subcutaneously (SC) with devazepide (DVZ; 1 ng/kg-1 mg/kg), an antagonist selective for the CCK-A receptor, or its vehicle, 0.5% carboxymethylcellulose (CMC). Thirty min after injection, rats were given access to the same liquid food for 60 min. DVZ increased food intake significantly. Furthermore, the effectiveness of a very low dose of DVZ (10 ng/kg) is strong evidence that the effect of DVZ was specific for CCK-A receptors. Three of the rats that increased food intake after DVZ were also tested with L-365,260, an antagonist selective for the CCK-B receptor (10 ng/kg-100 micrograms/kg). L365,260 did not increase food intake significantly. These results confirm and extend previous reports that CCK-A receptor blockade increases food intake after an oral preload. They do not, however, demonstrate a role for the CCK-B receptor in mediating the satiating effect of ingested food under the same experimental conditions.

The effects of the anorectics benzphetamine, chlorphentermine, clortermine, mazindol, phendimetrazine, and phenmetrazine on food intake were compared to the effects of d-amphetamine in rhesus monkeys given daily access to food pellets. The ability of these compounds to maintain intravenous self-administration under a fixed-ratio 10 schedule was also determined in rhesus monkeys. All drugs reduced food intake in a dose-related manner. d-Amphetamine was the most potent. Mazindol, chlorphentermine, phenmetrazine, and phendimetrazine were approximately 1/5 to 1/9 as potent as d-amphetamine while benzphetamine and clortermine were 1/14 and 1/20 as potent, respectively. Benzphetamine, mazindol, and phenmetrazine were self-administered above saline levels and were approximately equipotent. Chlorphentermine and clortermine were not self-administered and phendimetrazine was self-administered by only one of four monkeys at one dose. Thus, although all of the compounds were effective anorectics, chlorphentermine, clortermine, and phendimetrazine did not function as positive reinforcers. Since the ability of a drug to function as a positive reinforcer is related to its dependence potential, these three compounds might be less subject to abuse when used therapeutically. Within the group of 3 compounds that was self-administered, benzphetamine was relatively more potent as a positive reinforcer than as an anorectic. Therefore, this drug might be a less desirable compound for therapeutic use.