Motivational influences underlying prolactin-induced feeding in doves (Streptopelia risoria)

Prolactin (Prl) increases food consumption in ring doves (Streptopelia risoria) and may promote the hyperphagia exhibited by parent doves when provisioning young. These experiments tested whether Prl also enhances appetitive aspects of feeding behavior. Prl elevated pecking rates in food-restricted doves on a variable-interval (VI) reinforcement schedule and supported continued responding when doves were returned to ad-lib feeding. Prl-treated doves learned the key-pecking response when food intake was clamped at ad-lib levels exhibited before Prl treatment but not when given free access to food. Median break points on a progressive ratio schedule were 2-3 times greater in food-restricted doves than Prl-treated, food-clamped doves even though response rates were similar on VI schedules. These results indicate that Prl enhances appetitive aspects of feeding, although food restriction at the level imposed in this study was more effective in this regard.     

Central administration of ghrelin preferentially enhances fat ingestion

Ghrelin, a brain-gut peptide discovered from the stomach, stimulates growth hormone release, food intake, adiposity, and weight gain. Circulating ghrelin levels are modulated under conditions of positive and negative energy balance, however its effect on macronutrient selection is not known. The present experiment investigates the effect of ghrelin on single and two-diet feeding paradigms in high-carbohydrate (HC) and high-fat (HF) preferring rats. In the macronutrient selection test in which rats were given free access to either high-carbohydrate or high-fat diet, an intracerebroventricular (i.c.v.) administration of ghrelin potently enhanced fat intake over carbohydrate intake in both HC- and HF-preferring rats. In the diet preference test in which rats were given free access to both high-carbohydrate and high-fat diets simultaneously, an i.c.v. administration of ghrelin also preferentially enhanced fat consumption over carbohydrate in both HF- and HC-preferring rats. Intracerebroventricular administrations of galanin and neuropeptide Y enhanced fat and carbohydrate ingestion, respectively. Centrally administered ghrelin enhanced fat ingestion. These results provide further insights for the role of ghrelin in feeding behavior and the development of obesity.     

Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.     

Effects of 2-deoxy-D-glucose on schedule dependent and schedule induced behavior and ingestion at different body weights.

The effects of intraperitoneally administered 2-deoxy-D-glucose (2DG) at 0, 50, 150, 300 and 600 mg/kg, were studied in four experiments. Experiments 1 and 2 determined the effects of 2DG on schedule induced licking and drinking and schedule dependent lever pressing in rats maintained at 80% and ad lib free feeding body weights during 3 hr on an FI-1 min food reinforcement schedule. Experiments 3 and 4 evaluated the effects of 2DG on free access home cage food and water consumption under the same body weight conditions. Decreases in food and water consumption were observed under both feeding conditions when animals were reduced to 80% free feeding body weight. At ad lib feeding body weight, 2DG administration had no effects on licking, drinking, and lever pressing during FI-1 min scheduled food reinforcement or on free access home cage feeding and drinking. The effects of 2DG on ingestive behavior are discussed in terms of central and peripheral glucosensitive cells and the consequences of blocking glucose utilization at different body weights under different stimulus conditions.     

The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle.

Several reports indicate that central injection of galanin stimulates feeding, and that there is macronutrient specificity in this response. In addition, the galanin receptor antagonist, M40, reduces food intake when injected centrally. The nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (PBN) contain galanin receptors, and are involved in the control of food intake. Hence, we sought to compare the feeding response to galanin injection into these areas with that of third ventricle (3V) galanin injection. The feeding response to injection of galanin was greatest for the 3V. Hindbrain injection of galanin stimulated food intake only at the beginning of the dark period. NTS injection of M40 inhibited intake of a macronutrient diet in food-deprived rats, but was ineffective at reducing dark-onset feeding or deprivation-induced chow intake. 3V injection of M40 did not reduce deprivation-induced intake. PBN injection of galanin at dark onset had no effect in a group of fat-preferring rats. These results suggest that hindbrain galanin may contribute to feeding by inhibiting satiety, and that hypothalamic galanin receptors are involved with stimulation of intake. Furthermore, the absence of a consistent pattern of the stimulation of macronutrient intake suggests that galanin may not be a significant effector of macronutrient selection during individual meals.     

Effects of sibutramine on the appetitive and consummatory aspects of feeding in non-human primates

This study examined how sibutramine (0.06-4.0 mg/kg, i.m.), a clinically effective weight-loss medication which increases extracellular serotonin and norepinephrine levels, affected the appetitive and consummatory aspects of feeding of non-human primates. The effects were compared to the effects of the positive control dexfenfluramine (2.0-6.0 mg/kg, p.o.), which primarily increases extracellular serotonin levels. Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Sibutramine increased the latency to the first meal of the session in females, and decreased consummatory behavior without affecting other appetitive behavior in males and females. In contrast, dexfenfluramine, increased the latency to the first meal of the session, and decreased both appetitive and consummatory behavior in males and females. The behavioral mechanism by which sibutramine decreases food intake is distinct from other anorectic drugs, including dexfenfluramine, that have been tested in this paradigm.     

Effect of skeleton photoperiod and food availability on the circadian pattern of feeding and drinking in rats

Feeding and drinking behavior were measured in rats maintained under a 12:12 light-dark (LD) cycle or skeleton photoperiod (SPP). Feeding and drinking were closely associated during the normal LD cycle but under SPP conditions an increased feeding activity during the subjective day was not accompanied by an equivalent increment of water intake. This indicates a stronger coupling of drinking to the subjective night. A restriction of food availability to the subjective light phase did not cause an accompanying complete shift in drinking behavior. These results suggest that drinking is largely dependent on the influence of a circadian oscillator and this association is not disrupted by changes in feeding schedule. A change in food access to the subjective light phase caused partial but not permanent desynchronization between feeding and drinking behavior. Synchrony was reestablished within one day once food was available ad lib. Complete return to the original feeding and drinking patterning took 3 days. It is suggested that separate slave oscillators controlling feeding and drinking are governed by a hypothesized "master" circadian oscillator which remains definitely entrained to the original rhythm by the light pulses of the SPP condition.     

Opioids as facilitators of feeding: can any food be rewarding?

Palatability is one of the most rewarding aspects of consummatory behavior. Opioids, potent facilitators of intake of sweet and fat tastants, are thought to mediate hedonics of feeding. However, the rewarding context of consumption is not limited to palatability, and gratification can be achieved through other means, e.g., eating to satisfy hunger. The current review discusses the role of opioid peptides in food intake regulation by incorporating this expanded concept of feeding reward. We present evidence that, aside from increasing sugar/fat consumption, opioids propel the intake of diets whose gustatory value is low but are nonetheless consumed under circumstances allowing feeding gratification to occur. Opioids enhance reward-driven consumption by acting within the classical reward circuitry and also by signaling reward at sites that regulate other aspects of food intake, such as satiety and aversion. We conclude that, due to the complexity of neural and functional interactions, opioids are capable of enhancing pleasure of eating any food - palatable, bland or even aversive - making any meal into a more rewarding experience, despite possible consequences.     

Similarities in hypothalamic and mesocorticolimbic circuits regulating the overconsumption of food and alcohol

Historically, studies of food intake regulation started with the hypothalamus and gradually expanded to mesocorticolimbic regions, while studies of drug use began with mesocorticolimbic regions and now include the hypothalamus. As research on ingestive behavior has progressed, it has uncovered more and more similarities between the regulation of palatable food and drug intake. It has also identified specific neurochemicals involved in palatable food and drug intake. Hypothalamic orexigenic neurochemicals specifically involved in controlling fat ingestion, including galanin, enkephalin, orexin and melanin-concentrating hormone, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Research in Bart Hoebel's laboratory in conjunction with our own has shown that consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Both fat and ethanol intake are also regulated by dopamine and acetylcholine acting in mesocorticolimbic nuclei. This close relationship of fat and ethanol is likely driven in part by circulating lipids, which are increased by fat and ethanol intake, known to increase expression and levels of the neurochemicals, and found to promote further intake of fat and ethanol. Compellingly, recent studies suggest that these systems may already be dysregulated in animals prone to consuming excess fat or ethanol, even before they have ever been exposed to these substances. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse.     

Feeding and hypothalamic stimulation increase dopamine turnover in the accumbens

The hypothesis that the dopaminergic system plays a role in feeding behavior was tested in three experiments. First, microdialysis was performed in the nucleus accumbens (NAC) at 20 min intervals during free feeding in rats at 80% of normal body weight. Extracellular concentration of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) increased significantly during eating indicating an increase in DA turnover. Second, microdialysis samples were collected from the NAC during bar pressing with a) a signal light on and food available, b) the light on but no food available, c) neither light nor food. Only when food was available did extracellular DA, DOPAC and HVA increase significantly. This increase in DA turnover occurred in the accumbens but not in the ventral striatum. Third, electrical stimulation of the perifornical lateral hypothalamus (LH) that was capable of inducing feeding increased extracellular DA, DOPAC and HVA in the NAC. This occurred whether the animal had food to eat or not. The effect of LH stimulation on DA turnover resembled the effects of free feeding and operant feeding in Experiments 1 and 2. Perifornical LH stimulation did not increase dopamine turnover in the ventral striatum. The results show that perifornical LH stimulation activates the mesolimbic dopamine system and that dopamine release in the accumbens is involved in feeding. The increase in dopamine turnover outlasted the consummatory act. This suggests that accumbens dopamine may be related to sensory input, feeding reflexes, food reward or memory processes and not just to the consummatory act itself.     

Hypothalamic and hindbrain NPY, AGRP and NE increase consummatory feeding responses

Feeding behavior is comprised of both appetitive and consummatory responses to food. Appetitive responses include the motivated acquisition of food. Consummatory responses, including swallowing, are those that move the food from the mouth to the stomach. Intraoral delivery of liquid food bypasses the requirement for appetitive responses and has been used to examine consummatory responses directly in intact rats. In the present study, we administered neuropeptide Y (NPY), agouti-related protein (AGRP) and norepinephrine (NE), into the paraventricular nucleus of the hypothalamus (PVN) or into the fourth cerebral ventricle to examine their effects on the consummatory component of feeding behavior in the rat. To measure consummatory responses, milk (40% lactose free cow's milk diluted with water) was infused intraorally through a chronic cheek fistula (1 ml/min), using an alternating 5 min on − 1 min off schedule, until rejection occurred. We found that both hypothalamic and fourth ventricle injections of NPY, AGRP and NE significantly increased consumption of the intraorally-delivered milk. Our results indicate that the circuitry for modulation of consummatory ingestive responses includes NE, NPY and AGRP receptors operating in both hypothalamic and hindbrain sites.     

Meal patterning of rats with changes in day length and food availability

Feeding activity in rats is mainly nocturnal, with about 70–90% of the total daily intake eaten in the dark phase. During this phase, feeding has a typical biomodal pattern, i.e. a high level of feeding activity early and late in the night. The aim of the present study was to investigate the effects of temporary food restriction at dawn and dusk, and advanced light onset on the bimodal feeding pattern of male rats. It was found that suppression of food intake by restricting access to food or altering light onset act in radically different ways on the circadian meal patterning. It is argued that food restriction led to a general metabolic deficit, which was compensated by an increase in intake, especially after deprivation. Advancing light onset shifted the “dawn peak” of food intake to precede light onset. The results suggest that under these experimental conditions advancing light onset but not temporary food restriction can “reset” the circadian pacemaker.     

On the motivational deficits after medial hypothalamic lesions

After medial hypothalamic (MH) lesions, rats overeat when given free access to food and undereat when given limited access to food. The present experiments, designed to ascertain the specificity of appetite dysfunctions after MH lesions, indicated: (1) that rats with MH lesions, which do not adjust food intake appropriately during food deprivation, do drink normally when water deprived; (2) that the motivational deficit is apparent in instrumental situations using variable-interval and continuously reinforced schedules of reinforcement; and, (3) that rats with bilateral lateral hypothalamic (LH) lesions respond to food deprivation in a fashion similar to normal rats. These data support the idea that a discrete mechanism which controls the energization of feeding associated instrumental behaviors after food deprivation resides in the medial hypothalamus.     

Reinforcer-specificity of appetitive and consummatory behavior of rats after Pavlovian conditioning with food reinforcers

We examined the reinforcer-specificity of Pavlovian conditioning in the control of appetitive and consummatory behaviors in Pavlovian-to-instrumental transfer, cue-potentiated eating, and devaluation procedures. Rats received pairings of one conditioned stimulus with sucrose and another conditioned stimulus with maltodextrin. In Experiment 1, rats were also trained to earn sucrose for one instrumental response and maltodextrin for another. In a transfer test, the Pavlovian cues enhanced the rate of instrumental responding more when the food reinforcer predicted by the instrumental response and the Pavlovian cue were consistent than when they were inconsistent, but both cues enhanced both responses. In Experiment 2, sated rats' consumption of each food was potentiated in the presence of a cue for that food, but not in the presence of a cue for the other food. In Experiment 3, one food was devalued by pairing it with lithium chloride, prior to testing food consumption and food-cup directed behaviors. The food cues selectively controlled food-cup related behaviors, regardless of the presence of the devalued or nondevalued foods in the food cup. Together, these results are consistent with the view that conditioned cues modulate appetitive and consummatory behaviors with increasing levels of specificity. The closer an action comes to ingestion, the more it is controlled by sensory properties conveyed by learned cues. These data are discussed in the context of allostatic regulation of food foraging and intake.     

Alcohol as a Food: A Commentary on Richter

The present study examined the maintenance of voluntary alcohol intake in male Long-Evans rats. A microstructural analysis of consummatory behaviors (food, alcohol, water) was carried out using a computerized drinkometer system. In this sample of animals, there was no association (r = 0.07) between total food intake and total alcohol intake. There was no compensation for the extra calories ingested in the form of alcohol via a reduction in total food intake, or a reduction in food bout sizes associated with pre- or postprandial alcohol consumption. Further microstructural analyses determined that there were no significant difference between water and alcohol in terms of their distribution in relation to food (non-, pre-, or postprandial bouts). Of the total of 586 bouts of fluid intake analyzed, 45.6% were consumed postprandially, with a similar number (43.2%) consumed nonprandially. A comparison of the size of food bouts associated with different fluid bout types (pre- or postprandial) indicated that food bouts were the same size regardless of whether they were accompanied by water or alcohol. A final analysis determined that 55% of the total daily alcohol intake was consumed postprandially, and that the sizes of non-, pre-. or postprandial fluid bouts were significantly different for water vs. alcohol. Post hoc pairwise comparisons found that alcohol postprandial bouts were significantly larger than all types of water bouts. Alcohol and water bouts ranged in size from <0.5 ml to >5.5 ml There was a significant difference in the distribution of bout sizes with more alcohol bouts at the high end of the distribution. Only 24% of the water bouts were >2.5 ml compared to 48.4% of the alcohol bouts. The results of this study demonstrate that rats organize their consummatory behavior in many discrete, short bouts. There were considerable individual differences in alcohol preference, alcohol-bout frequency, duration, and size, as well as the prandial distribution of bouts. All of these variables together produce the “pattern” of alcohol intake in individual animals, and is likely to influence the level of intoxication achieved. Although rats do not dissociate their alcohol intake from normal feeding patterns, alcohol bouts occurring postprandially are significantly larger than other bouts of fluid consumption, suggesting that animals perceive the pharmacological effects of and are affected by the alcohol they consume. In animals with a preference for alcohol solutions, it is unlikely that alcohol is consumed as a food.     

The short-term feeding behavior of growing pigs fed foods differing in bulk content

We investigated the effects of foods of different bulk on the short-term feeding behavior (STFB) of 16 individually housed pigs. The three foods used had different bulk contents [low-control (C), medium-70% wheat bran (WB), and high-70% sugar beet pulp (SBP)]. We expected the different intakes of the foods to be reflected in differences in STFB. Three hypotheses were developed based on ideas about the way in which a physical constraint to intake could arise. H(1): there would be less diurnal variation in feeding on high-bulk foods that limit food intake. H(2): feeding patterns on the bulky foods would be less flexible than those on C. H(3): a change in food type would result in food intake and STFB being rapidly altered to become appropriate to the new food. There were significant differences in food intake and STFB between the foods as intended. Pigs fed WB and SBP spent longer eating and had a slower feeding rate (FR) than pigs fed C. H(1) was rejected, as there was no difference in diurnal variation in intake between the foods. Feeding was not extended into the night on WB and SBP and the proportion of feeding that occurred during the night was the same for all three foods. H(2) was supported, as pigs fed WB and SBP were unable to maintain food intake and performance when time of access to the feeder was reduced. There was no adaptive change in STFB. H(3) was supported as a change from WB or SBP to C, or vice versa, caused a rapid change in STFB so that it became appropriate to the new food. It is concluded that physical constraints to food intake, caused by food bulk, may bring about changes in STFB and that they are important for the regulation of intake of such foods.     

Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.

Central amygdaloid nucleus lesions in rats had no effect on recovery of preoperative body weight and food consumption levels. The brain damaged rats also recovered preoperative levels of water consumption as rapidly as control rats but then developed a mild but persistent hypodipsia. The experimental rats also drank less than control rats when food deprived and showed marginally reliable decreases in 0.1% quinine solution consumption and latency to consume a novel food. There was no detectable lesion effect on 0.1% saccharin solution consumption, exploration of a novel environment or formation of a learned taste aversion. It is suggested that the central amygdaloid nucleus has a role in mediating the relationship between food and water intake and in some taste mediated consummatory behavior.     

The effect of cholecystokinin-octapeptide on food intake and consummatory behavior in lactating rats.

Rats are less sensitive to the satiating effect of CCK-8 during some reproductive states such as estrus and proestrus, and in ovariectomized rats following the administration of estradiol and progesterone. The sensitivity of rats to CCK-8's effect on food intake decreases as lactation progresses. During lactation, prolactin and progesterone levels are elevated. Implantation of ectopic pituitaries increases prolactin levels in males and females as well as progesterone levels in females. To evaluate whether or not prolactin elevation modifies CCK's effect on feeding, we studied the effect of CCK-8 on food intake during the early dark cycle in male and female rats implanted with ectopic pituitaries. As previously demonstrated, prolactin levels were elevated in both male and female pituitary-implanted rats and progesterone levels were elevated in the female rats. CCK-8 inhibited food intake in sham-operated male rats, but did not reliably decrease early dark cycle food intake in sham-operated or pituitary-implanted female rats or pituitary-implanted male rats. Thus an elevation in prolactin levels does not appear to modify the effect of CCK-8 on food intake in female rats. We also evaluated the effect of CCK on consummatory and maternal behavior in lactating rats. CCK-8 altered the meal patterns of lactating rats primarily by decreasing the rate of food consumption and increasing the latency to the first meal. The latency to the first meal of rats receiving CCK was increased during early and mid-lactation and the PW period, but not during late lactation compared to that of the saline-injected rats. CCK-8 did not modulate any of the maternal behaviors studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake

Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.     

Regulation of feeding behavior in the prepubertal female rat.

Responses to challenges of long-term regulation of feeding behavior were compared between adult and weanling female rats. Adulteration of a high fat diet with NaCl caused both adult and weanling rats to reduce their food intake, but neither group refused to eat. Food deprivation for 24 hr was followed by an increase in feeding for both adult and weanling animals during a period when food intake is normally very low. Continued limited food access to 2 hr during the light period was compensated for by an increase in the normal food intake for this period for both adult and young female rats. It was observed that both adult and weanling rats showed a marked preference for the more dilute glucose solution when given a choice. In addition, both groups maintained a constant caloric intake during presentation of the glucose solutions by adjusting their intake of a solid food source. In each challenge of long-term regulation of feeding behavior, the response of weanling animals was as good or superior to that shown by adults. It is concluded that weanling female rats regulate their feeding just as adults to maintain long-term energy balance. It was also observed that bilateral lesions placed in the ventromedial hypothalamus (VMH) at 21 days of age resulted in reduced daily food intake and retarded body weight gain. Furthermore, young rats with VMH lesions failed to respond to 24 hr of food deprivation or limited food access. These data suggest an important role for the VMH in the long-term regulation of feeding in young rats.