Cholecystokinin elicits the complete behavioral sequence of satiety in rats.

Observed and scored the behavior of intact rats and rats with chronic gastric fistulas during a 60-min test period when they were offered liquid diet after 17 hr of food deprivation. The same 5 adult male Sprague-Dawley rats were employed in 2 experiments. Intact Ss and Ss with closed fistulas displayed a specific behavioral sequence at the end of each meal: They stopped eating, engaged in grooming and exploration for a short time, and then rested or slept. Thus, a fixed behavioral sequence characterized satiety in Ss. Although the behavioral sequence of satiety was fixed, the cessation of feeding was not a sufficient condition for the appearance of the rest of the sequence: Quinine adulteration of the liquid diet stopped sham feeding but did not elicit the complete sequence. Intraperitoneal injection of the intestinal hormone cholecystokinin during sham feeding, however, elicited the complete sequence of satiety. The observation that cholecystokinin not only stopped feeding but elicited the complete sequence of satiety supports the hypothesis that endogenous cholecystokinin is a satiety signal for the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of cholecystokinin on meal size and intermeal interval in the sham-feeding rat.

Gave 8 Sprague-Dawley male albino rats with gastric fistulas liquid food with the fistula closed (normal feeding) or open (sham feeding) after 3 hrs of food deprivation. Meal size (MS) was larger, latency to rest (LR) after a meal was longer, and intermeal interval (IMI) was shorter during sham feeding than during normal feeding. The putative satiety signal cholecystokinin (CCK, 20% pure) decreased MS and LR and increased IMI during sham feeding. After CCK (30 U/kg) the MS, LR, and IMI were the same during sham feeding as during normal feeding. The synthetic octapeptide (OCT) of CCK, which has the known biological actions of the complete hormone, reproduced the effects of CCK (30 U/kg) on MS and LR but not on IMI. The CCK and OCT were also tested for their ability to serve as a UCS for the formation of a conditioned taste aversion (CTA) in 10 3-hr food-deprived sham-feeding rats. The OCT did not serve as a UCS for a CTA in the same sham-feeding conditions in which OCT produced normal MS and LR. Impure CCK (30 U/kg), however, did serve as a UCS for a CTA under these conditions. Results are consistent with the hypothesis that CCK produces satiety in rats. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some characteristics of feeding during streptozotocin-induced diabetes in the rat.

Injected 24 male Sprague-Dawley albino rats with a buffer solution or 25-45 or 50-60 mg/kg of streptozotocin. 4-9 days after 50-60 mg. of streptozotocin Ss showed abbreviated intermeal intervals. There was also a lack of proportionality in intermeal interval duration to size of the preceding meal. This result probably accounts for the hyperphagia which develops at 4-6 days and increases over 2 wk. Such effects were not seen in the lst 3 days, even though the Ss were glucosuric and polydipsic within 24 hr. of streptozotocin treatment. In contrast, decreases in basal feeding rate and in meal size did begin to develop in the 1st 3 days of diabetes. It is suggested that aversion to the diet develops immediately on insulin deficiency, but that the satiety deficits and hyperphagia in chronic diabetes are secondary to considerable changes in body composition. (41 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypoxia inhibits gastric emptying and gastric acid secretion in conscious rats

This study examines the effects of hypoxia in the gastric function in conscious rats which adapted to a meal-feeding schedule, that allowed free access to a high protein (HP) diet (550 g casein/kg diet, Exp.1,2 and 4), a normal protein (NP) diet (200 g casein/kg diet, Exp.3) or a nonpurified rat (NPR) diet (Exp. 5 and 6) for 4 h every day for 2 wk. In Exp. 1, after 4 h of consuming the HP diet, rats were exposed to 7.6 or 10.5% O2 normobaric hypoxia. Hypoxia delayed the excretion of urinary urea for 12 h. In Exp.2 and 3, when rats were exposed to 7.6%O2 after 4 h of consuming the HP diet and exposed to 10.5% O2 after 4 h of consuming the NP diet, respectively, a significant delay in gastric emptying was found in the hypoxic rats. In Exp. 4, when rats were exposed to 7.6 O2 hypoxia after 4 hr of eating the HP diet, the plasma gastrin concentration in the 7.6% O2 hypoxic rats was 2.3-fold that of the normoxic rats after 6 h of hypoxia. Furthermore, when rats that did not consume any HP diet on the day of the experiment were exposed to 7.6 or 10.5% O2 hypoxia, the plasma gastrin concentration was higher in both hypoxic groups than in the normoxic group after 3 and 6 of hypoxia. In Exp. 5, rats that were not fed the NPR diet on the day of study were exposed to 7.6 or 10.5% O2 hypoxia for 3 h after pylorus ligation. Hypoxia inhibited the secretion of gastric acid and elevated the plasma gastrin concentration. In Exp. 6, unfed rats that had been consuming the NPR diet were exposed to 7.6% O2 hypoxia for 3 h after pylorus ligation and were orally administered HCl. The rise of the gastrin concentration due to hypoxia was completely inhibited by oral HCl. These results demonstrate that hypoxia inhibits gastric emptying and gastric acid secretion and that the inhibitory effect of hypoxia on gastric acid secretion stimulates gastrin release through positive feedback regulation.     

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)     

Effects of gastric loads and food deprivation on subsequent food intake in suckling rats.

In 4 experiments, a total of 478 suckling Charles River rats were subjected to deprivation periods of 6-8 hrs. Intake following deprivation was greater in deprived than in nondeprived Ss but did not increase with increasing deprivation. Gastric loads of NaCl solutions depressed subsequent intake; 3% NaCl was more effective than .9% NaCl. Other gastric loads of varying osmotic and caloric values also depressed subsequent intake. In order of increasing effectiveness in depressing intake, the gastric loads were protein hydrolystate, heavy cream, water, milk, lactose, glucose, and corn oil. Effectiveness was unrelated to osmotic or caloric value of the load. Gastric fill and, possibly, some property of carbohydrate appeared to be important determinants of satiety in the S. (22 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)     

Mathematical analysis of energy regulatory patterns of normal and diabetic rats.

Analysis of feeding patterns indicated that diabetic (alloxan) hyperphagia is characterized by doubling of meal sizes with no change in feeding frequency. 10 normal and 10 diabetic male Long-Evans rats were used. Correlation of meal sizes and intermeal intervals did not provide any systematic relationships for either normal or diabetic Ss. When equations of the general form Y = A + Bcos(X) were fit to successive satiety ratios (postmeal interval-meal size), diabetic Ss showed significantly lower A coefficients, reflecting a lower average level of satiety, as well as significantly lower B coefficients, reflecting less systematic variability in the satiating value of food around the average level. It is concluded that the major regulatory deficit in diabetic animals is a chronic reduction in the long-term signal of body nutrient repletion. (19 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)     

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)     

Either a paradigm shift or no mental measurement: the nonscience and the nonsense of The Bell Curve

We have shown previously that intravenous infusions of insulin, known to induce glucoprivic hunger, and of insulin combined with glucose, known to induce satiety, produce in the VMH and PVN of Wistar rats monoaminergic changes that differ from those related to spontaneously occurring hunger and satiety, while the genetically obese Zucker rat is totally resistant to the behavioural effects of insulin and insulin + glucose infusions. In the present study, the impact of these infusions on VMH and PVN monoamines in obese Zucker rats was assessed using microdialysis. Monaminergic changes (increase in DOPAC and 5-HIAA and decrease in DA and 5-HT) were quite similar in obese rats to those we found in normal rats when insulin was infused. In contrast, changes in 5-HT or DA in response to insulin and glucose were quite different in the Zucker rat. Monoaminergic changes related to meals were more dramatic in the Zucker rat and so were able to reverse the background changes produced by the insulin infusion. These data confirm the idea that the effect on monoamines of spontaneously occurring hunger and satiety is different from the effect on monoamines by insulin and glucose-induced hunger and satiety. The results show disturbances of the obese Zucker rat related both to insulin and to hypothalamic monoamines that may be involved in the hyperphagia and obesity of this model.     

Gastric versus duodenal feeding and gastric tonometric measurements

OBJECTIVE: To compare the influence of gastric and postpyloric enteral feeding on the gastric tonometric PCO2 gap (tonometric PCO2 - PaCO2). DESIGN: A prospective, clinical trial. SETTING: Two intensive care units in a university hospital. PATIENTS: Twenty patients undergoing mechanical ventilation and enteral feeding without catecholamines, sepsis, or sign of hypoxia. INTERVENTIONS: Patients were randomized to receive feeding through the tonometer (gastric group), or through a postpyloric tube (postpyloric group). MEASUREMENTS AND MAIN RESULTS: The patients received tube feeding at a rate of 50 mL/hr during 4 hrs. Baseline measurements included: mean arterial pressure, heart rate, tonometric parameters, arterial gases, and arterial lactate concentration. Except for lactate concentration, these measurements were repeated after 1 and 4 hrs of enteral feeding and 2 hrs after stopping enteral feeding. During the study, arterial pH and PaCO2 did not change. During enteral feeding, the PCO2 gap increased in the gastric group from a mean of 7+/-5 to 17+/-14 (SD) torr (0.9 0.7 to 2.3+/-1.9 kPa) (p< .O01) and did not change in the postpyloric group (5+/-5 to 3+/-1 torr [0.7+/-0.7 to 0.4+/-0.1 kPa]). Two hours after stopping enteral feeding, the PCO2 gap was still increased in the gastric group (15+/-9 vs. 7+/-5 torr [2.0+/-1.2 vs. 0.9+/-0.7 kPa]) (p < .01). CONCLUSION: The results indicate that gastric enteral feeding increased the PCO2 gap. However, postpyloric enteral feeding does not interact with gastric tonometric measurements and should be used when using gastric tonometry in enterally fed patients.     

Ventromedial hypothalamic hyperphagia in the hypophysectomized weanling rat.

Previous findings that ventromedial hypothalamic (VMH) lesions in weanling rats lead to obesity only after a delay of several weeks suggests either that the VMH is (a) undeveloped and not yet functioning; or (b) capable of functioning in weanlings, but inoperative for some reason. The present study demonstrates that 17 hypophysectomized weanling rats, which otherwise eat very little and grow at a markedly reduced rate, show hyperphagia with rapid onset following VMH lesions. Results support G. Kennedy's view that the presence of high levels of growth hormone in the weanling is responsible for VMH inactivity, either by eliminating the usual metabolic satiety signals and/or via a direct effect of the hormone on the VMH. Growth hormone involvement is suggested to account for the greater ease in producing hypothalamic hyperphagia in female than in male rats. (18 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of mesulergine treatment on diet selection, brain serotonin (5-HT) and dopamine (DA) turnover in free feeding rats

1. The effects of mesulergine, a 5-hydroxytryptamine (5-HT) receptor antagonist with dopamine (DA) agonistic properties, on rats diet selection over a seven day period and on 5-HT and DA turnover was studied. 2. Three groups of male Wistar rats were individually caged and ad libitum fed with a standard (SD) and 50% sweet carbohydrate enriched diet (CED). Food intake was measured daily 4 hrs and 24 hrs after i.p. injections of mesulergine (1 and 3 mg/kg) or vehicle. 5-HT and 5-HIAA in hypothalamus (Hy), Striatum (St) and hippocampus (Hi) as well as DA and DOPAC in (Hy) and (St) were assayed at the 8th day of the experiment. 3. There was a dose dependent increase of SD consumption 4 hrs after mesulergine treatment while the CED remained unchanged with total food intake dose dependently increased as a consequence. At 24 hrs measurements SD consumption was increased only for the dose of 1 mg/kg of mesulergine, while a dose dependent decrease of CED intake was observed. Total food intake was unchanged for the dose of 1 mg/kg and decreased with the dose of 3 mg/kg consequently. A dose dependent decrease of rats body weight was observed too. 4. A significant increase of 5-HIAA/5-HT ratio in (Hy) and (St) for the dose of 1 mg/kg and in (Hi) for the dose of 3 mg/kg with no changes of DA turnover were found. 5. The above data suggest a dual mode of action of mesulergine presented as a short term hyperphagia due to simultaneous antiserotonergic and dopaminergic activity and long-term hypophagia due to long-term agonistic effects of dopaminergic neurons.     

Effects of adrenalectomy on hyperphagia induced by the 5-HT1A receptor agonist 8-OH-DPAT and 2-deoxy-D-glucose in rats

Effects of adrenalectomy on the 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT)- and 2-deoxy-D-glucose (2-DG)-induced hyperphagia were investigated in rats. Prior adrenalectomy completely inhibited 2-DG-induced hyperphagia, although it did not affect increases in food intake elicited by 8-OH-DPAT. These results suggest that 8-OH-DPAT-induced hyperphagia is independent of the adrenal hormone, corticosterone while 2-DG-induced hyperphagia is closely related to corticosterone.     

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)     

Paraventricular hypothalamic lesions and medial hypothalamic knife cuts produce similar hyperphagia syndromes.

Compared the hyperphagia/obesity syndrome produced by paraventricular hypothalamic (PVH) lesions and that produced by medial hypothalamic (MH) knife cuts in adult female Sprague-Dawley rats. Each treatment produced hyperphagia and overweight on a chow diet, although the PVH effect was less than the knife cut effect. Each treatment also produced qualitatively similar ingestive responses to unpalatable quinine- and sucrose octaacetate-adulterated diets and to palatable dextrose and fat diets during the dynamic and static weight-gain phases. The PVH lesions and MH cuts disrupted day/night feeding patterns and elevated water intakes but not water/food intake ratios. However, PVH lesions, unlike MH cuts, did not increase emotional reactivity. The relation of the PVH syndrome to the classic hypothalamic hyperphagia syndrome is discussed. Also considered is the neuroanatomical substrate responsible for the PVH hyperphagic effect. (66 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atropine fails to block the overconsumption of sugar solutions by hypothalamic hyperphagic rats.

Adult female Sprague-Dawley rats given bilateral parasagittal knife cuts in the medial hypothalamus (VMH group) were hyperphagic and became obese on a chow diet, compared with sham-operated controls. VMH Ss also overconsumed, relative to controls, sucrose and glucose solutions during 30-min/day tests. Pretreating VMH and control Ss with atropine methyl nitrate (1.0, 5.0, or 10.0 mg/kg) reduced their intake of the sugar solutions in 3 of 5 experiments, and in all experiments it suppressed their 24-hr chow intake. However, VMH Ss continued to drink more of the sugar solutions than the controls after all atropine treatments, and in 3 of 4 experiments their hyperphagia on the chow diet was not blocked by the atropine. Results do not support the hypothesis that vagally stimulated insulin release or other cholinergically mediated cephalic responses of digestion are essential for the expression of hypothalamic hyperphagia and finickiness. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concurrent inhibition of sexual behavior, but not brain [–3H]estradiol uptake, by progesterone in female rats.

In 7 experiments with ovariectomized female Sprague-Dawley rats, chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 μg) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hrs. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 μg to 6 μg or 10 μg offset this inhibition. High doses inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hrs prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into 5 injections (.2 mg) every 4 hrs. Results of 2 experiments in which progesterone did not inhibit the uptake or retention of [–3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the CNS is not to interfere with the binding of estradiol. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Leptin Receptor

Leptin is a fat cell-derived satiety factor that regulates food intake and energy expenditure. Its effects are mediated by interactions with the leptin receptor (Ob-R) that is alternatively spliced to encode at least five isoforms(a-e), which are distributed in a wide range of tissues including the hypothalamus. Ob-R is a member of cytokine receptors and involves the JAK-STAT signal transduction system. We found Ob-R mutations in Zucker fatty rats and obese Koletsky rats and demonstrated that Ob-R dysfunction brings around hyperphagia and obesity. However we and others have not found any Ob-R mutation in human obese subjects.