Development of bingeing in rats altered by a small operant requirement.

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.

Environments predicting intermittent shortening access reduce operant performance but not home cage binge size in rats.

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.

Baclofen-induced reductions in optional food intake depend upon food composition.

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.

2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats.

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.

Assessing binge eating. An analysis of data previously collected in bingeing rats.

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.

Fat emulsion composition alters intake and the effects of baclofen.

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.

Effect of 2-hydroxyestradiol on binge intake in rats.

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.

Reinforcing efficacy of fat, as assessed by progressive ratio responding, depends upon availability not amount consumed.

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.

Baclofen, raclopride, and naltrexone differentially affect intake of fat/sucrose mixtures under limited access conditions.

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.

Access conditions affect binge-type shortening consumption in rats.

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-type behavior in rats consuming trans-fat-free shortening.

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.

Baclofen, raclopride, and naltrexone differentially reduce solid fat emulsion intake under limited access conditions.

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.

Liquid sucrose bingeing in rats depends on the access schedule, concentration and delivery system.

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.

Effects of baclofen on operant performance for food pellets and vegetable shortening after a history of binge-type behavior in non-food deprived rats.

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.

Effects of dietary fats on bone health in advanced age.

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.

mCPP-induced hypophagia in rats is unaffected by the profile of dietary unsaturated fatty acids.

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.

Food intake in rats is unaffected by the profile of dietary essential fatty acids.

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.

Effects of limited access to a fat option on food intake and body composition in female rats.

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.

Different preferences for oils with similar fatty acid profiles.

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.