Genetic versus hypothalamic obesity: Studies of intake and dietary manipulations in rats.

Studied feeding behavior in 4 experiments with a total of 86 Zucker rats. Ad-lib food and water intakes were significantly greater for the genetically obese rats (fatties) than for their nonobese littermates. The ratio of water intake per gram of food intake was not different for the 2 groups. The ability to regulate caloric intake was then tested in 4 groups of rats: genetically obese, ventromedial hypothalamic lesioned (VMH) obese, sham operated, and normal controls. In response to caloric dilution and quinine adulteration the genetically obese Ss behaved more like normal Ss than like VMH-lesioned Ss. Sensitivity to quinine increased with age in the Zucker fatty. The fact that Ss with genetic obesity and Ss with hypothalamic obesity displayed different behaviors suggests that obesity is not merely a unitary disorder. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ovarian and hypothalamic obesity syndromes in the female rat: Effects of diet palability on food intake and body weight.

Results of 2 experiments with 96 CFE female rats show that both ovariectomy and hypothalamic knife cuts produced hyperphagia and obesity in Ss. The ovarian obesity, however, unlike hypothalamic obesity, was virtually independent of diet palatability. Ovariectomized Ss became obese on quinine-adulterated diets which completely blocked hypothalamic obesity, and they displayed little further weight gain when given a high-fat diet which greatly potentiated hypothalamic obesity. Ovarian and hypothalamic obesity were also found to be additive irrespective of diet condition when both surgical treatments were combined in the same S; that is, ovariectomy increased the food intake and body weight of knife-cut Ss given the quinine or high-fat diet. In contrast to their dissimilar feeding effects, ovariectomy, hypothalamic cuts, and the combined surgeries did not differentially alter the aversion to a 0.01% quinine solution. Results indicate that ovarian obesity and hypothalamic obesity represent 2 different feeding disorders and are mediated by separate neural mechanisms. The functional nature of these disorders is discussed in light of recent body weight set point interpretations. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetically obese (ob/ob) mice are predisposed to gastric stress ulcers.

In Exp I, 20 adult male genetically obese (ob/ob) mice and 20 lean littermate controls were food deprived and subsequently physically restrained at normal room temperatures. Obese Ss became hypothermic and developed gastric stress ulcers. Lean Ss maintained normal body temperatures and did not form gastric ulcers. In Exp II, 5 male obese and 4 lean littermates were used to test the effects of noradrenaline (NA) during restraint, and 5 obese and 5 lean mice were used to test the effects of NA alone. It was expected that in lean, but not in obese, Ss that NA would induce an increase in O? consumption beyond that induced by initial restraint. O? consumption was measured during food deprivation and restraint. Obese and lean Ss had parallel metabolic responses, with obese Ss using significantly less O? at all times. The predisposition to formation of gastric ulcers is a new phenotypic expression of the ob/ob genotype. The pathogenesis of this susceptibility appears to be related to a genetic disturbance in heat production. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food motivation and body weight levels in hypothalamic hyperphagic rats: A dual lipostat model of hunger and appetite.

Compared the food and water motivations of 26 normal and 29 hyperphagic female Carworth CFE rats using barpressing performance on continuous reinforcement, VI, and fixed-ratio schedules. Under conditions of food or water deprivation, hyperphagic Ss displayed normal barpressing rates for food or water when their body weights were limited to preoperative or control levels but subnormal barpressing rates when they were tested at obese body-weight levels. Under nondeprived conditions, dynamic hyperphagic Ss barpressed more than controls for a palatable milk diet, while obese hyperphagic Ss worked at control levels for this diet. The findings suggest a dual lipostat model of hunger and appetite to explain feeding and body weight regulations in normal and hypothalamic hyperphagic animals. (62 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diet palatability modulates sham feeding in VMH-lesion and normal rats: Implications for finickiness and evaluation of sham-feeding data.

Examined the capacity for taste cues to modulate the food intake of 24 ventromedial hypothalamic (VMH) and normal Long-Evans rats. Ss were implanted with a chronically indwelling gastric cannula and sham fed (cannula open) or normally fed (cannula closed) liquid diets varying in sucrose content. VMH Ss were maintained at control body-weight levels. For both groups, the discrepancy in consumption between sham and normal feeding situations depended on the sweetness of the diet. The implications of this finding for studies using sham feeding to assess putative feeding control signals are discussed. VMH lesions exaggerated the sensory control of food intake. Under sham-feeding conditions, increases in the sweetness of the diet led to disproportionately large increments of food intake in VMH Ss relative to controls. Data support the existence of a finickiness component in the VMH syndrome and allude to the nature of the physiological disturbance underlying this behavior change. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic systemic administration of 5-HT on food intake and body weight in rats

The effects of chronic peripheral administration of 5-HT on food intake and body weight was investigated. In normal male Wistar rats, normal female Wistars, obese Zucker males, ovariectomised Wistar females, or normal Wistar males free fed a cafeteria diet, suppression of the creeping weight gain typical of control animals is observed. In females, this effect is not dependent on the local hormonal environment, because intact and ovariectomised females showed similar responses to treatment. One sex difference is that the weight suppressive effect in males is accompanied by an anorectic effect, whereas this anorectic effect is absent in females. Thus, although reduced food intake may partially explain the suppression of weight gain in males, in females it must be due to other, perhaps metabolic, effects. It is possible that these metabolic effects may also occur in males, suggesting one possible explanation of why the effect was typically larger in males than females.     

Behavioral and neurochemical effects of neonatal administration of monosodium {l}-glutamate in mice.

Studied the feeding behavior, activity level, and thermoregulatory ability of 117 CL-1 mice made obese by neonatal administration of monosodium {l}-glutamate (MSG). The degree of obesity and other characteristics of the syndrome depended on age, diet, and housing condition. Carcass fat determinations demonstrated the presence of obesity in all MSG Ss; however, body weight was elevated over control levels only in adult mice caged in groups. Group-housed MSG Ss also failed to increase food intake in response to food deprivation and were both hypoactive and hypothermic. Individually caged MSG Ss showed normal activity levels and body temperature, an attenuated response to food deprivation, and an enhanced response to a high-fat diet. Since MSG obesity may be the consequence of damage to the dopamine-rich arcuate nucleus of the hypothalamus, a 2nd goal was to measure central catecholamines and examine any changes in the MSG S's behavioral responses to catecholaminergic drugs. Ss treated with MSG sustained some loss of hypothalamic dopamine, but no systematic relation between central catecholamines and behavioral aspects of the syndrome could be discerned. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opiates and medial hypothalamic knife cuts cause hyperphagia through different mechanisms.

In Exp I, male Sprague-Dawley rats were given bilateral parasagittal medial hypothalamic knife cuts (KCs) or a sham procedure and fed a high-fat diet. KC and sham-operated Ss were approximately equally sensitive to the suppressive effects of naloxone (0.1–20 mg/kg, subcutaneously [sc]) on food intake. Ketocyclazocine (0.1–20 mg/kg, sc) generally increased daytime food intake in sham-operated Ss; in contrast, the normal hyperphagia of KC Ss was in most cases either unchanged or decreased by ketocyclazocine. In Exp II, neither diet composition nor hypothalamic KCs significantly affected the feeding responses to naloxone or the stimulatory effects of butorphanol tartrate (0.1–20 mg/kg, sc). It was hypothesized that the differential effects of ketocyclazocine in KC and sham-operated Ss were a consequence of the sedative effects of the drug combined with the elevated baseline of the KC Ss. This hypothesis was supported by Exp III, which showed that ketocyclazocine also reduced nocturnal intake in unoperated Ss and that butorphanol increased intake. That feeding responses to naloxone and butorphanol were essentially unchanged by hypothalamic KCs suggests that the opioid feeding system is independent of the longitudinal feeding inhibitory pathway believed to be involved in KC-induced hyperphagia. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of feeding in rats: II. Independent ingestive behavior.

In 4 experiments, Charles River rat pups 3 days of age and older consumed large quantities of milk, sucrose, and wet mash when the Ss were placed in warm containers in which one of these diets had been spread on the floor. The volume of Ss" intake was directly related to the severity of food deprivation. Ingestive behavior occurred in the early part of the 30-min test, but later in the test, Ss stopped feeding and became quiescent. Their ingestive behavior thus resembled that of adults in (a) the motor aspects of feeding responses (licking and lapping), (b) the dependency on deprivation for intake, and (c) the pattern of intake termination. However, in Exp IV, when diet was restricted to a small area of the test container, young Ss consumed little diet. They did not appear able to direct or focus their ingestive responding. It was not until 9–12 days of age that Ss successfully consumed milk from a localized source. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperphagia in rats with experimental diabetes mellitus: A response to a decreased supply of utilizable fuels.

In 2 experiments with male Sprague-Dawley rats, alloxan-diabetic rats were hyperphagic when fed diets containing little fat, but they ate normal amounts of food when given diets rich in fat. Normal Ss increased food intake to the same degree when the caloric density of their diet was decreased by reducing the content of fats or carbohydrates in isocaloric amounts. Diabetic Ss did not respond substantially to changes in caloric density of their diet which were produced by altering the content of dietary carbohydrates, but they systematically increased food intake as the amount of fat in their diet was reduced. Diabetic Ss ate normal amounts of a high-fat diet despite continued loss of nutrients in urine and persisting impairments in glucose utilization, fat storage, and liver glycogen deposition. Findings suggest that hyperphagia in experimental diabetes mellitus is a compensatory response to a lack of utilizable fat fuels rather than the result of a metabolic disturbance per se. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in fatty acid composition in rat adipose tissue induced by dietary obesity

The aim of the study was to evaluate the effects of cafeteria feeding on the composition of fatty acids in retroperitoneal fat pad and also to determine what happens to fatty acids when rats previously fed the cafeteria diet are returned to regular rat chow. The study of the post-cafeteria rats enabled us to determine the effects of dietary induced excess weight in the absence of artefactual interferences from the diet because these rats, unlike the cafeteria obese rats, ate the same diet as controls. In response to cafeteria feeding there were increases in the majority of adipose tissue fatty acids. However, significant decreases were observed in the relative proportions of 18:2n-6 and in two related n-6 polyunsaturated fatty acids (18:3n-6 and 20:3n-6), as well as in 16:1. In the post-cafeteria obesity model the previous dietary influence on fatty acid composition was still evident. The maintenance of both the high levels and proportions of 18:1 and the decrease of 16:1 percentage in the post-cafeteria rats argues in favour of an alteration in the activity of the elongation metabolic pathway. Certain changes affecting polyunsaturated fatty acid adipose depot composition of obese rats, mainly the decreased levels of 18:2n-6, are long lasting and could be related to the maintenance of the obese status. On the whole, although the fatty acid composition of adipose tissue is influenced by the composition of the diet, there are some differences in both the maintenance of the effects and also in the selectivity of adipose tissue for the different fatty acids of obese and lean rats.     

Trigeminal deafferentation and ingestive behavior in rats.

For studying the role of orosensory input in the control of ingestive behavior, 46 male albino Wistar rats were subjected to varying degrees of trigeminal deafferentation in 2 experiments. Somatosensory branches that convey touch, temperature, and pain from the oral cavity were sectioned selectively, and muscles of mastication and taste afferents were left intact. Severe intake deficits were produced, including aphagia, adipsia, and prolonged hypophagia, accompanied by a corresponding decrease in body weight. The deficits were proportional to the extent of deafferentation and were most severe when upper and lower portions of the mouth were affected. Although somatosensory impairment affected the organization of the consummatory response, all Ss could bite, chew, and lick. Analysis of feeding patterns showed that minimally (mandibular) deafferented Ss compensated for the consummatory inefficiency by increasing meal duration but failed to initiate meals at the normal rate, thus keeping food intake below normal levels. Results suggest that oral somatosensory input is critical for the mechanisms that regulate ingestive behavior. (45 ref)) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suckling behavior and intake control in the developing rat pup.

Studied the behavioral development of suckling and intake control in 2 experiments with Charles River CD strain rat pups. Ss were observed at the initiation, during the course, and at the termination of suckling from their anesthetized mothers. Diet was delivered intraorally through a fine tongue cannula which enabled control of timing and volume. The control of diet intake and the behavior at termination of suckling showed correlated changes from 5 to 20 days of age. When deprived of suckling (and food and water) for 8 hr, 5- and 10-day-old Ss consumed large volumes of diet (10% of body weight or greater) and terminated suckling only in the presence of extreme gastrointestinal filling. These Ss were immediately lethargic and slept after intake termination. Five-day-old Ss persisted in reattaching to the nipple when manually stimulated; 10-day-old Ss eventually refused to reattach. In contrast, 20-day-old Ss consumed more moderate volumes of diet (5% of body weight). These Ss also remained awake for a period after feeding and engaged in the exploratory and grooming activities characteristic of adult rats at the termination of feeding. These observations demonstrate major changes in suckling behavior during development. They suggest that intake control processes shift from indirect to direct and become more effective and specifically food intake related in older pups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reactivity of normal and VMH-lesion rats to quinine-adulterated foods: Negative evidence for negative finickiness.

Conducted 2 experiments with ventromedial hypothalamic (VMH) and normal rats to examine (1) whether the anorexic properties of quinine depend on quinine's sensory properties or on its postingestive effects, and (2) whether VMH rats overrespond to quinine adulteration. These issues were examined by comparing the feeding adjustments to quinine by VMH and normal male Long-Evans rats in a sham-feeding situation and under normal feeding circumstances, on Ss' initial exposure to this drug. In Exp I, 17 Ss received VMH lesions or sham lesions before being sham fed with various concentrations of quinine. In Exp II, 18 lesioned or sham-lesioned Ss were fed unadulterated food for 12 days, followed by a meal adulterated with quinine, 2 days of pure mash, and 1 day of quinine. Quinine caused significant depression of food intake in Ss. Little evidence exists for a conclusion that VMH rats are more reactive than normals to quinine-adulterated foods. Results suggest that major food intake perturbations of VMH rats are in response to hedonically positive dietary manipulations. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats define different body weights depending on palatability and accessibility of their food.

Normal adult Long-Evans rats lived on powdered diets adulterated to contain as much as 1.6% quinine sulfate, on a palatable high-fat diet, or in Skinner boxes with 45-mg Noyes pellets available on FR schedules as high as FR-256. They maintained lower body weights over periods of months in proportion to the percentage of quinine adulteration or the FR. Ss on the high-fat diet overate as much and gained weight as rapidly as Ss recovering from food deprivation, and became moderately obese. Ss having become lean or obese contingent on the palatability or accessibility of their diet defended body weight by eating more in the cold, less when force-fed by gavage, and more to restore weight after food deprivation. Yet on chow they restored and defended body weights typical of Ss whose diet had been confined to commercially prepared chow. Results are inconsistent with motivational models that rigidly distinguish drive from incentive, that treat body weight changes as evidence for failure to regulate energy balance or body weight, or that rely exclusively on deprivation of food or reduction of body weight for definitions of need for calories. Instead, caloric homeostasis in rats may incorporate ecological constraints. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of obesity and set point on taste responsiveness and ingestion in humans.

Two experiments, with a total of 120 undergraduates, investigated the relationships among degree of obesity, nearness to set point for adipose tissue mass, and responsiveness to taste. In Exp I, Ss rated milkshakes varying in sweetness intensity. Overweight and normal weight Ss did not have significantly different detection thresholds or preference ratings. However, overweight Ss worked longer than normals to obtain their most preferred substance. Exp II varied the ease of tasting the milkshake. Preference and food intake of moderately overweight Ss were significantly more influenced by tastes that they found positive and negative than was the preference of normal weight or obese Ss. The ease of ingesting the taste substance also significantly influenced preference and food intake of the moderately obese only. Nearness to set point, operationally defined as weight stability for 2 yrs, had no significant effects. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estrus- and ovariectomy-induced body weight changes: Evidence for two estrogenic mechanisms.

Estrogenic modulation of body weight in female rats is usually thought to result indirectly from estrogenic modulation of food intake. However, present data from 5 experiments with 79 female albino rats suggest that estrogens influence body weight by at least 2 mechanisms, 1 of which is independent of changes in food intake. When Ss were ovariectomized (Ovx) and food intake was limited to preoperative levels, Ovx Ss nonetheless gained large amounts of body weight. Although Ovx Ss gained more weight than controls on the same amount of food, during 33 hrs of food deprivation Ovx and control Ss lost weight at the same rate, indicating that the prefasting metabolic rates of the 2 groups were similar. During the 1st 40 days after surgery, the ano-nasal lengths of Ovx Ss increased twice as fast as that of intact Ss, which suggests a mechanism for the gradual increase in weight induced by Ovx. The weights of intact Ss followed a regular 4-day cycle during ad lib feeding, but when the estrus-associated decrease in food intake was prevented, the cyclic weight changes were altered. Thus estrogens appear to regulate body weight by modulation of food intake and modulation of ano-nasal growth or other metabolic processes. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypothalamic knife cuts: Effects on eating, drinking, irritability, aggression, and copulation in the male rat.

Describes 2 experiments with a total of 43 male hooded rats. In Exp. I, Ss with parasagittal knife cuts that separated the medial from the lateral hypothalamic areas (a) became hyperphagic, hyperdipsic, obese, and irritable; (b) did not change their level of aggressive responses against mice; and (c) copulated at an impaired rate or not at all. In Exp. II, 2 groups of Ss were subjected to coronal cuts restricted between the fornices at levels either anterior or posterior to the ventromedial hypothalamic nuclei. Most of the anterior-cut Ss increased their food and water intake, and some became irritable. Of the posterior-cut Ss, none increased and 1/2 decreased their food intake, some became hyperdipsic, and 1 became irritable. Neither of the coronal-cut groups changed levels of aggressive or sexual responses. It is concluded that the mediolateral hypothalamic connections are important for eating, irritability, and copulation. (42 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of gastric reduction surgery on consummatory behavior in the rat.

When the gastric capacity of 10 male Sprague-Dawley rats were reduced by partitioning a portion of the cardiac region of the stomach, they ate significantly less than did 10 sham-operated Ss during restricted (2-hr) access to either a liquid or a solid diet. Experimental Ss not only ate less during 2-hr food access, they appeared to satiate more quickly than sham-operated Ss. In contrast, when food was continuously available, the food intake of experimental Ss did not differ from that of controls. In addition, the water intake of experimental Ss was not significantly different from that of controls under either ad-lib or restricted access. Thus, reducing stomach capacity by partitioning a portion of the cardiac region appears to produce a relatively specific disruption of feeding behavior under conditions of restricted access. Implications for the study of gastric feeding mechanisms and for the surgical treatment of morbid obesity in humans are discussed. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vagotomy produces learned food aversions in the rat.

Two experiments, each with 28 female Long-Evans rats, examined whether some of the depression in food intake observed in rats with vagotomy could be due to the development of aversions to the foods eaten after surgery. In Exp I, significant aversions developed to the specific novel diet consumed after vagotomy, results indicating that the symptoms associated with vagotomy (hypophagia, weight loss, discomfort) can serve as effective UCSs in the acquisition of learned food aversions. Exp II compared vagotomized Ss consuming familiar laboratory chow with those consuming a novel diet. In contrast to the novel diets, learned aversions to the familiar chow did not develop and hypophagia was less persistent and severe. It is concluded that learned food aversions can contribute to the appetite and weight loss exhibited by vagotomized animals. Consideration of the conditions under which these aversions arise after vagotomy surgery may allow for the design of studies so as to minimize the aversions and thereby separate these nonspecific effects from direct regulatory deficits produced by vagotomy. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)