Vagotomy blocks hypothalamic hyperphagia in rats on a chow diet and sucrose solution, but not on a palatable mixed diet.

Adult female Sprague-Dawley rats were given ventromedial hypothalamic parasagittal knife cuts (VMH treatment) or control surgery (Con treatment), followed 10 days later by subdiaphragmatic vagotomy (Vag treatment) or sham vagotomy (Sham treatment). The hyperphagia and obesity produced by the VMH cuts to Ss on a chow diet was completely blocked by vagotomy (VMH-Vag group). Vag also inhibited the VMH Ss' overconsumption of a 20% sucrose solution during 1-hr/day and 24-hr/day tests, which contrasts with the effects of atropine treatment. However, when offered a selection of palatable foods (cookies, sweet milk, high-fat ration) in addition to chow, VMH-Vag Ss overate and gained considerably more weight than did the Con-Vag or the Con-Sham Ss. Con-Vag Ss, on the other hand, gained less weight than Con-Sham Ss on the palatable diet. Results indicate that intact subdiaphragmatic vagi are not essential for the expression of VMH hyperphagia and finickiness, and they therefore question the role of vagally mediated cephalic responses in the hypothalamic hyperphagia syndrome. On the other hand, results indicate that in brain-intact animals Vag suppresses the development of diet-induced obesity. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vagotomy Blocks Hypothalamic Hyperphasia in Rats on a Chow Diet and Sucrose Solution, but Not on a Palatable Mixed Diet: Correction.

Reports an error in the original article by A. Sclafani, P. Aravich and M. Landman (Journal of Comparative and Physiological Psychology, 1981, Vol. 95, No. 5, 720-734). Table 3 contains several errors in the mean and standard error values for the second and third groups. The correct table is provided. (The following abstract of this article originally appeared in record 1982-09338-001): Adult female Sprague-Dawley rats were given ventromedial hypothalamic parasagittal knife cuts (VMH treatment) or control surgery (Con treatment), followed 10 days later by subdiaphragmatic vagotomy (Vag treatment) or sham vagotomy (Sham treatment). The hyperphagia and obesity produced by the VMH cuts to Ss on a chow diet was completely blocked by vagotomy (VMH-Vag group). Vag also inhibited the VMH Ss' overconsumption of a 20% sucrose solution during 1-hr/day and 24-hr/day tests, which contrasts with the effects of atropine treatment. However, when offered a selection of palatable foods (cookies, sweet milk, high-fat ration) in addition to chow, VMH-Vag Ss overate and gained considerably more weight than did the Con-Vag or the Con-Sham Ss. Con-Vag Ss, on the other hand, gained less weight than Con-Sham Ss on the palatable diet. Results indicate that intact subdiaphragmatic vagi are not essential for the expression of VMH hyperphagia and finickiness, and they therefore question the role of vagally mediated cephalic responses in the hypothalamic hyperphagia syndrome. On the other hand, results indicate that in brain-intact animals Vag suppresses the development of diet-induced obesity. (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)     

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)     

Multiple knife cuts between the medial and lateral hypothalamus in the rat: A reevaluation of hypothalamic feeding circuitry.

In 2 experiments single or multiple sets of bilateral knife cuts were made in a total of 73 female CFE rats just lateral to the ventromedial hypothalamus (VMH) and/or just medial to the lateral hypothalmus (LH). The lateral VMH knife cuts by themselves produced greater hyperphagia and obesity than did the medial LH cuts. The lateral VMH knife cuts also significantly increased food intake and body weight in Ss previously given bilateral cuts along the medial LH border. Findings indicate that the feeding inhibitory fibers responsible for the hyperphagia syndrome do not project from the VMH to the LH, and this calls for a reevaluation of hypothalamic circuitry. It was also discovered that sham surgery in 7 Ss had a significant suppressive effect on the hyperphagia syndrome produced by hypothalamic knife cuts. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Thiamin deprivation in ventromedial hypothalamic hyperphagic rats: Anorexia, specificity of food aversion, and a dietary consideration.

In 3 studies, the anorexic consequence of thiamine deprivation was investigated in ventromedial hypothalamic (VMH) hyperphagic CD male rats under either high-fat or low-fat (HF and LF, respectively) thiamine-free diet conditions. The LF diet maintained feeding significantly longer in thiamine-deprived VMH Ss than in intact Ss, whereas the HF diet sustained feeding in thiamine-deficient intact Ss and accelerated anorexia onset in vitamin-B1-deprived VMH Ss. This effect was noted under both ad lib and pair-feeding conditions. Thiamine-deprived VMH Ss subjected to weight control developed anorexia sooner than intact Ss regardless of the diet employed. The VMH Ss fed an HF diet failed to resume feeding after thiamine readministration, which is interpreted as a permanent aversion to this diet. The relation between dietary intake and conditioned taste aversion is discussed with reference to the VMH and intact rats. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Failure to obtain sex differences in development of obesity following ventromedial hypothalamic lesions in rats.

Gave 24 male and 24 female albino Charles River rats either a high-fat or a ground-food diet following ventromedial hypothalamic or sham lesions. After 63 days on 1 diet, diets were reversed for 27 days. Over 63 days (a) lesioned Ss of both sexes showed a significant increase in weight over their controls, (b) Ss on high fat gained more weight than those on ground food, and (c) there was no difference between the sexes in weight gain. When diets were reversed, lesioned Ss now on ground food maintained about the same weight as before reversal, while Ss switched to the high-fat diet rapidly increased their body weight to a point near that of Ss originally on the high-fat diet. Data indicate that there is no sex difference in weight gain following ventromedial lesions. It is suggested that previously reported differences result from (a) insufficient periods of observation, (b) offering unpalatable diets, or (c) the use of random-bred strains which increases variability of animal size and lesion placement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperphagia and obesity produced by parasagittal and coronal hypothalamic knife cuts: Further evidence for a longitudinal feeding inhibitory pathway.

Hyperphagia and obesity are produced by parasagittal knife cuts through the medial hypothalamus and by coronal knife cuts through the posterior hypothalamus. Results of the present series of experiments with 91 female CFE rats indicate that the 2 types of cuts produce their overeating effect by severing the same neural pathway. Exp I demonstrated that unilateral parasagittal knife cuts combined with contralateral coronal cuts in either the posterior hypothalamus or the midbrain significantly increased food intake and body weight. Exp II revealed that bilateral parasagittal cuts and bilateral coronal cuts in the hypothalamus produced qualitatively similar effects on food intake, diurnal ingestive pattern, finickiness, and amphetamine anorexia. The 2 types of cuts differentially altered water intake, however. In Exp III, coronal cuts in the posterior hypothalamus, like parasagittal cuts in the medial hypothalamus, increased the food intake and body weight of Ss previously given bilateral parasagittal transections through the lateral perifornical region. The neuroanatomy and neurochemistry of the longitudinal feeding inhibitory pathway suggested by these results are discussed. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Effect of a quinine-adulterated diet upon body weight maintenance in male rats with ventromedial hypothalamic lesions.

Reports results of 3 experiments with a total of 100 male Sprague-Dawley rats. Ss offered a quinine-adulterated diet after receiving either ventromedial hypothalamic or sham lesions displayed nearly identical periods of anorexia before maintaining their body weight at a stable but reduced level. When starved prior to surgery to a body weight below this reduced maintenance level, both ventromedial hypothalamic and control Ss displayed an initial period of rapid weight gain on the quinine-adulterated diet. When subsequently offered only this diet for an 8-wk period, both groups, after castration, maintained the same reduced level of body weight. It is concluded that ventromedial hypothalamic animals overeat and become obese on palatable diets but defend the same lower weight level as controls when challenged with unpalatable diets. Impairment of a mechanism setting the upper, but not the lower, weight limit is suggested to be responsible for the greatly expanded range of body weights generated in the ventromedial hypothalamic animal by manipulation of diet palatability. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventromedial syndrome: The rat's "finickiness" results from the obesity, not from the lesions.

6 obese, finicky female hooded rats with lesions of the hypothalamic ventromedial nucleus (VMH) and 7 sham-lesioned controls progressively lost weight on an unpalatable diet until at a critical basal level they increased their intake to prevent further loss of weight. The critical basal body weight was similar in both groups and showed no change in the controls when they were subsequently lesioned and retested. At weight levels below the critical basal level the feeding behavior of lesioned and unlesioned Ss was similar, and finickiness could be demonstrated only when body weight exceeded it. The basal level bore no relation to the plateau level of body weight reached by Ss on a free diet. Suggestions that the VMH excites as well as inhibits feeding seem untenable in view of the failure of VMH lesions to impair defense of body weight in the nonobese rat. (17 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)     

Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin.

Assessed long-term changes in food and water intake, body weight (BW), and skeletal growth following bilateral hypothalamic microinfusions of 5,7-dihydroxytryptamine (DHT; 6 or 12 μg) in 16 female hooded rats. The analysis of ingestive behavior included assessment of photoperiodic effects and responsivity to alterations in dietary composition. The neuroanatomical and neurochemical selectivity of the serotonergic depletion was documented by regional spectrofluorometric analysis for serotonin (5-hydroxytryptamine, 5-HT), dopamine, and norepinephrine. Results indicate that, substantial depletion of 5-HT occurred in the septum, hippocampus, and hypothalamus of the DHT (12 μg) group. During feeding of a high-fat diet, the 5-HT-depleted Ss exhibited a long-lasting and stable hyperphagia that led to an increase in BW. Because BW increased in the absence of increased skeletal growth or intestinal weight, it is concluded that the increased BW reflected increased adiposity. Overall results provide evidence of an inhibitory role of 5-HT in food intake and point to the importance of maximizing both neurochemical and neuroanatomical selectivity. (46 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)     

Effects of diet on feeding and body weight regulation during pregnancy and lactation in the golden hamster (Mesocricetus auratus).

Conducted 3 experiments with 90 female golden hamsters to test the hypothesis that the weight loss shown by lactating hamsters constitutes a regulated weight loss. Results support the hypothesis, showing that prefattened overweight Ss lost more weight from the time of mating to the end of lactation than did unmanipulated controls. However, the weight loss during lactation was reduced by giving Ss access to a high-fat diet, a result indicating that a portion of the lactational weight loss may also be regulated by the diet provided. When lactating Ss were given access to a fractionated diet consisting of pure fat, pure carbohydrate, or 45% protein, they increased their proportional intake of both protein and fat but not of carbohydrate. Studies show that hamsters differ from rats in their pattern of energy regulation during pregnancy, lactation, and the postsuckling period. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chonically reduced body weight in rats sustaining lesions of the lateral hypothalamus and maintained on palatable diets and drinking solutions.

12 male Holtzman rats sustaining lateral hypothalamic (LH) lesions regulated their body weight at a reduced level when maintained for 1 mo postlesion upon a wet mash diet. Thereafter, for a period of 84 days, half of these Ss were offered a high fat diet, whereas the remaining Ss continued to receive wet mash. A series of palatable drinking solutions were also offered. Body weight remained at reduced levels relative to 8 intake controls regardless of the diet offered, even under conditions of high fluid intake generated by the palatable drinking solutions. Results contradict the interpretation of E. J. Mufson and R. S. Wampler (see record 1973-00428-001) that the lower body weight observed in LH-lesioned animals is secondary to lesion-produced "finickiness" and/or dehydration resulting from hypodipsia. Rather, a primary shift in the set point for body weight appears to underlie the reduced levels of weight maintenance in LH-lesioned animals. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice

The C57BL/6 (B6) mouse is more sensitive to the effects of a high-fat diet than the A/J strain. The B6 mouse develops severe obesity, hyperglycemia, and hyperinsulinemia when fed this dietary regimen. This study was conducted to determine the effects of dietary fat and sucrose concentrations on body composition and intestinal sucrase (EC 3.2.1.48) and maltase (EC 3.2.1.20) activity in these two mouse strains. High-fat diets, regardless of sucrose content, resulted in significant weight gain, higher body fat, and lower body protein and water content in both strains of mice. The shift toward higher body fat and lower protein and water content was far greater in the B6 strain. Low-fat, high-sucrose diets resulted in lower body weight in both strains, as well as significantly greater body protein content in B6 mice. Analysis of intestinal sucrase showed that the enzyme was less active in B6 mice when the diet was high in sucrose. Both sucrase and maltase had lower activity in the presence of high dietary fat in both mouse strains. The percent reduction of intestinal enzyme activity due to dietary fat was similar in both strains. The B6 mouse exhibits disproportionate weight gain and altered body composition on a high-fat diet. This coupled with the reduced body weight and increased body protein on a low-fat, high-sucrose diet suggests that factors-relative to fat metabolism rather than sucrose metabolism are responsible for obesity.     

Delayed hyperphagia and increased body length after hypothalamic knife cuts in weanling rats.

In 2 experiments a total of 23 4-wk-old female Carworth albino rats received parasagittal hypothalamic knife cuts. 11 Ss served as sham-operated controls. Polydipsia began in the experimental Ss right after surgery, but hyperphagia, obesity, and excessive nose-anal length did not begin until after the Ss were 7-8 wk old. The delayed onset appears to await some maturational event that is required for the expression of hypothalamic obesity. It appears likely that puberty is the critical maturational event. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Growth and development of the kidneys, heart and liver in S 5B/P1 and Osborne-Mendel rats fed high or low-fat diets

Male Osborne-Mendel (OM) and S 5B/P1 rats were overfed from birth to 24 or 105 days. The effects of feeding a diet with 44 per cent or 3 per cent (w/w) fat, supplementary feeding during the suckling period, and reduced litter size, on body weight and on the weight and cellularity of the heart, liver and kidneys were evaluated. Three overfeeding techniques were used: (1) feeding a high fat diet, (2) reducing litter size, (3) force-feeding from 1-24 days. The overfeeding technique which exerted the greatest effect on growth was feeding a high-fat diet. In comparison to OM rats that suckled dams fed the low-fat diet, body weight as well as organ weight, DNA, protein and lipid were significantly elevated in 24-day-old OM rats that suckled dams fed the high-fat diet. In comparison to OM rats not overfed, the organs of the rats fed the high-fat diet contained significantly more cells at both 24 and 105 days, except for the heart which by 105 days contained more protein, but not DNA. Liver weight and growth in S 5B/P1 rats was similar, regardless of dietary manipulation. Compared to S 5B/P1 rats that suckled dams fed the low-fat-diet, kidneys were 12 per cent larger at 24 days and 19 per cent larger at 105 days in rats that suckled dams fed the high-fat diet and were thereafter fed a high-fat diet. Hearts of the latter rats were larger than the former rats at 24 days, but not at 105 days.