F.H.E. Wojnicki

Limited Access to a Dietary Fat Option Affects Ingestive Behavior But Not Body Composition in Male Rats

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.

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

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.

Baclofen reduces fat intake under binge-type conditions

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.

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.

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.

Binge eating in rats with limited access to vegetable shortening.

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 GABAB 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.

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.

Effects of drugs on food- and cocaine-maintained responding III: Dopaminergic antagonists

Abstract The effects of three dopamine (DA) antagonists (SCH23390, pimozide, and chlorpromazine), with various degrees of selectivity for D1 and D2 receptors, and an agonist (the cocaine analog, CFT) were studied on responding maintained under a multiple fixed-ratio (FR) 30 food, FR30 cocaine (1–100 µg/kg per injection) delivery, with an interposed 10-min time-out (TO), schedule in rhesus monkeys. The effects of each drug depended upon the unit dose of cocaine. With an intermediate (10 µg/kg per injection) unit dose of cocaine, each antagonist decreased rates of responding maintained by either event in a dose-related manner. At higher (56–100 µg/kg per injection) unit doses of cocaine, antagonists generally increased and then decreased both food- and cocaine-maintained responding in a dose-related manner. These increases appeared to result from the blockade of non-specific rate-decreasing effects of self-administered cocaine, questioning their relevance to the reinforcing effects of cocaine. The results failed to support a role for pharmacological selectivity in this rate-decreasing effect of cocaine, as both D1 and D2 antagonists were able to reverse the effect. In contrast, CFT decreased cocaine-maintained responding at doses less than those that decreased food-maintained responding, and failed to shift the cocaine dose-effect function to the left. These results, together with previous work, suggest that agonists can selectively decrease drug-seeking behavior.

Effects of drug history on the acquisition of responding maintained by GBR 12909 in rhesus monkeys

The reinforcing effects of cocaine have been associated with its actions at the dopamine reuptake site. Previous studies have shown that selective dopamine reuptake inhibitors can attenuate cocaine self-administration in animals, suggesting that they may serve as pharmacotherapeutic agents. In order to assess the potential reinforcing effects of one of these agents, the acquisition and maintenance of GBR 12909 self-administration were studied in different groups of rhesus monkeys (Macaca mulatta) that were either experimentally naive or experienced with respect to the self-administration of cocaine or GBR 12909. Lever-pressing was maintained under a multiple FR30 schedule with alternating components of either food or drug presentation. Experimentally naive monkeys failed to self-administer low doses of GBR 12909 (3–30 µg/kg per injection). However, after a history of cocaine self-administration, GBR 12909 (56 µg/kg per injection and then 30 µg/kg per injection) maintained numbers of drug deliveries similar to those maintained by cocaine. When another group of experimentally-naive monkeys was initially exposed to GBR 12909 self-administration, 56 µg/kg per injection failed to maintain responding. However, subsequent exposure to 100 µg/kg per injection established GBR 12909 self-administration, and high levels of responding were sustained later when the unit dose was decreased to 30 µg/kg per injection. In monkeys with prior experience with cocaine self-administration (∼75 sessions) unit doses of either 30 µg/kg per injection or 56 µg/kg per injection GBR 12909 maintained responding. In another group of monkeys with a more extensive history of cocaine self-administration (∼320 sessions), unit doses of either 10 µg/kg per injection or 30 µg/kg per injection GBR 12909 maintained responding. These results show that drug-maintained responding can be established with higher unit doses of GBR 12909. After exposure to these higher, more effective doses of GBR 12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to support drug-maintained responding.

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.