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This study examined the involvement of caudal brainstem projections of the hypothalamic paraventricular nucleus (PVN) in the medial hypothalamic (MH) hyperphagia-obesity syndrome. Experiment 1 demonstrated that a unilateral parasagittal knife cut in the MH combined with a contralateral coronal knife cut in either the ventrolateral pons (vP) or ventrolateral medulla (vM) significantly increased food intake and body weight in adult female rats. Overeating and overweight were also produced by a unilateral MH knife cut combined with a contralateral oblique cut under the nucleus of the solitary tract and dorsal motor nucleus of the vagus complex (NST/DX). In contrast, an MH cut × dorsolateral medullary cut combination did not increase food intake or body weight compared to a MH cut alone or sham surgery. Experiment 2 demonstrated that the hyperphagia/obesity effect of MH × vP knife cuts was comparable to that obtained with bilateral PVN lesions, but less than that produced by bilateral MH knife cuts. Bilateral vP cuts also increased body weight but the effect was less than that obtained with the other experimental treatments. Feeding the rats a high-fat diet rather than chow potentiated the hyperphagia and obesity syndromes produced by the various lesion conditions. Taken together, these findings suggest that the medial hypothalamic hyperphagia and obesity syndrome is due, in part, to damage to PVN projections to the caudal brainstem, the NST/DX complex in particular. The functional significance of this PVN-hindbrain “feeding” pathway and the identity of extra-PVN components of the hyperphagia-obesity syndrome remain to be established.

Adult female rats were allowed to self-select their diet from separate sources of fat, protein, and carbohydrate (starch). Other rats were fed a composite diet that matched the nutrient composition chosen by the self-selecting rats (50% fat, 28% protein, 22% carbohydrate) or a low-fat, high-carbohydrate chow diet. Half of the rats in each diet condition were given access to a 32% sucrose solution for 30 days. Sucrose availability increased total caloric intake (approximately 20%) and body weight gain in all three groups compared to control groups not fed the sucrose solution. The selection animals compensated for their sucrose intake by reducing their fat intake, and to a lesser degree, their starch intake; protein intake was the least affected by sucrose availability. The selection rats consumed less sucrose than the chow-fed rats and displayed a smaller increase in weight, relative to controls, than the chow-fed rats. These differences were attributed to the high-fat intake of the selection animals since similar results were obtained with the rats fed the composite diet. In particular, both the selection and composite diets produced mild obesity in the absence of sucrose. The results demonstrate that sucrose-induced overeating and overweight is not an artifact of restraining the diet choices of rats to a pure sugar and a nutritionally complete diet.

Bilateral parasagittal knife cuts were placed between the medial and lateral hypothalamus of adult male and female guinea pigs. In both sexes, the knife cuts increased food intake, water intake, and body weight relative to control animals given sham surgery. The results demonstrate that hypothalamic hyperphagia and obesity can be produced in the guinea pig as in other species.

The palatability of glucose, sucrose, maltose and polysaccharide (Polycose) was assessed by examining the consummatory response of nondeprived female rats to equicaloric or equimolar solutions of these saccharides. Both 30-min one-bottle acceptance and 30-min two-bottle preference tests were conducted: initial (3-min) lick rates were also recorded. At low molar concentrations the relative palatability of the saccharides was ordered as follows: Polycose greater than maltose greater than sucrose greater than glucose. At higher concentrations the rats were more attracted to sucrose than to Polycose; however Polycose remained more palatable than maltose at all but the highest concentration. In the one-bottle tests gram solute intakes varied as a function of percentage concentration, and was not influenced by saccharide type or solution osmolarity. The results along with other recent findings indicate that rats can taste starch-derived polysaccharides and find them quite palatable.

Dietary obesity and dietary leanness were produced in adult male rats by feeding them either an assortment of palatable foods, or an unpalatable quinine-adulterated diet. When deprived of food the dietary obese rats initially showed little change in wheel running activity but as their weight fell to below normal levels they displayed a terminal burst of activity similar to that seen in normal-weight control subjects. Dietary lean rats, on the other hand, increased their wheel running activity at an accelerated rate, relative to normal-weight controls, when food deprived. Expressing the activity data as a function of percentage normal body weight eliminated these group differences. The results demonstrate that body weight must fall to some relatively fixed, i.e., diet independent, critical level before activity increases during a fast. Therefore, as measured by deprivation-induced activity, dietary obese, dietary lean, and normal-weight rats do not equally defend their particular weight levels.

Female rats made hyperphagic by parasagittal hypothalamic knife cuts overate a palatable milk diet by greatly increasing their meal size, while meal frequency was only slightly increased. Reducing the palatability of the diet by quinine or salt adulteration decreased to normal levels the total intake and meal size, but not meal frequency of hyperphagic rats. The disruption in the diurnal feeding pattern displayed by the hyperphagic rats was relatively unaffected by diet palatability changes. The results are discussed in terms of the short and long term regulatory deficits thought to be responsible for the hypothalamic hyperphagia syndrome.

The taste preference thresholds of adult female rats for polysaccharide (Polycose), maltose, and sucrose were compared. The nondeprived animals were given 24-hr two-bottle preference tests (saccharide solution vs. water) and, starting at 0.008%, the saccharide concentration was increased daily. The rats first preferred the Polycose solution to water at 0.01% (0.0001 M), the maltose solution to water at 0.09% (0.0025 M), and the sucrose solution to water at 0.09% (0.0026 M). Thus, on a molar basis the rats' Polycose threshold was 25 to 26 times lower than their maltose and sucrose threshold. It was postulated that the low taste threshold for polysaccharides allows the rat to detect starch which, unlike sugar, is very low in solubility.

The taste preferences of adult female rats for solutions of five different carbohydrates were evaluated using brief (3-min) two-bottle preference tests. At the lowest concentration tested (0.03 molar) the order of preference was Polycose greater than maltose greater than sucrose greater than glucose = fructose. Whereas at the highest concentrations tested (0.5 or 1.0 molar) the preference order was sucrose greater than maltose greater than or equal to Polycose greater than glucose greater than fructose. Thus, at low concentrations starch-derived polysaccharides (Polycose) are more palatable to rats than are sugars. These findings are consistent with the hypothesis that rats have separate taste receptors for sugars and for starch-derived polysaccharides. The fact that maltose is the most preferred sugar at low concentrations is attributed to its stimulation of "polysaccharide" taste receptors.

Following ovariectomy, adult female rats did not increase their food-reinforced bar pressing during 30-min tests, but they responded significantly more frequently for food than did control animals during 2- and 24-hr bar-press tests. Meal pattern data obtained during the 24-hr test demonstrate that ovariectomy increases meal size and decreases meal frequency, although the reduction in the number of meals did not fully compensate for the alteration in meal size. These findings suggest that ovariectomy does not increase the motivation to initiate a meal, but does result in the taking of a larger meal. The implication of these findings to body-weight set-point interpretations of ovarian obesity are briefly discussed.

Subdiaphragmatic vagotomy suppresses food intake and water intake in normal rats. Since human patients report some nausea and discomfort following vagotomy, the present study assessed the aversive consequences of vagotomy in rats using a conditioned taste aversion paradigm. Rats were given a total subdiaphragmatic vagotomy or sham vagotomy, and were then maintained on either plain water (Vag-Water and Sham-Water groups) or a novel cherry solution (Vag-Cherry and Sham-Cherry groups). When subsequently tested for their water vs. cherry preferences on postoperative days 6, 16, and 26, the Vag-Cherry group displayed a greater aversion to the cherry solution than did the remaining three groups. This result suggests that vagotomy produces visceral malaise in rats which may contribute to the feeding and drinking suppressive effects of the surgery.

The preference of adult female rats for aspartame (L-asparty L-phenylalamine methyl ester) was measured using 24 hr/day and 30 min/day two bottle preference tests. At aspartame concentrations that humans find sweet (0.0125% to 0.05%) the rats failed to prefer aspartame to water. At higher concentrations (0.1% to 1.0%) half (n = 11) of the rats tested displayed mild (64%) to moderate (83%) aspartame preferences. The other half of the rats were indifferent or avoided the aspartame. Even at the most preferred concentration (1.0%) the rats' aspartame preference was much less than their preference for saccharin or sucrose, and they showed little increase in total fluid intake when given the aspartame solution. The results indicate that aspartame is not very palatable to rats, and suggest that it has little or no sweet, i.e., sucrose-like, taste to rats as it does to humans.

Jejunoileal bypass (JIB) surgery reduces food intake and body weight in obese humans and rats. Human bypass patients report visceral discomfort following surgery, and the present study assessed the aversive consequences of JIB in rats using a conditioned taste aversion paradigm. In Experiment 1 rats given a cherry-flavored solution immediately after JIB surgery subsequently displayed a strong aversion to the cherry flavor compared to Bypass and Sham-Bypass control groups. Rats in Experiment 2 were familiarized with cherry solution prior to surgery and they did not display an aversion to the solution after receiving a JIB. In Experiment 3, Bypass rats who developed a cherry flavor aversion after JIB subsequently lost this aversion following reconnection of their intestinal tract. The rats in Experiment 4 displayed an aversion to a saccharin-flavored chow that was eaten shortly after JIB surgery, although the aversion was not as pronounced as that obtained with the cherry solution. The results suggest that JIB produces a persisting malaise in rats that may contribute to the feeding and weight inhibitory effects of the operation.

Bilateral parasagittal knife cuts were made in the hypothalamus of rats at lateral planes 0.5, 1.0, or 1.5 mm from the midline. Cuts through the ventromedial hypothalamus (VMH) at L-0.5 produced the hyperphagia syndrome and did not significantly depress wood gnawing. Cuts just lateral to the VMH at L-1.0 also produced the hyperphagia syndrome but depressed wood gnawing below control levels. Cuts along the medial edge of the lateral hypothalamus at L-1.5 produced a mild hypophagia-hyperphagia syndrome and completely blocked wood gnawing behavior. The findings suggested the possibility that specific hypothalamic neural pathways may control gnawing behavior.

Rats with ventromedial hypothalamic lesions displayed a reduced sensitivity to dilute (5 or 7%) glucose solutions. The lesioned animals were less responsive to the food suppressive effects of glucose ingestion, and they drank less dilute glucose when food deprived compared to controls. The VMH lesioned rats, on the other hand, appeared normally sensitive to concentrated (20 or 33%) glucose solutions. They suppressed their feeding in response to glucose intubation, and they consumed more concentrated glucose solution than did controls, which is consistent with the hyperphagia effects of the lesions. The nature of the neural impairment responsible for these lesion effects is discussed.

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

There is now extensive evidence that jejunioleal bypass (JIB) surgery reduces food intake in obese patients, and that in most cases this is the primary cause of their postoperative weight loss. Associated with the reduced food consumption are other behavioral changes, including alterations in meal patterns, appetite ratings, taste responsiveness, and food-related attitudes. Experimental animal research indicates that JIB surgery also reduces food intake in obese rats and alters their feeding patterns. The hypophagia and weight loss produced by the surgery in rats is dependent upon both the degree and type of obesity. The exact mechanism(s) by which JIB surgery suppresses food intake remains to be determined, although recent animal research implicates both visceral malaise and overstimulation of the lower ileum as contributing factors.

Surgical manipulations of the gastrointestinal system can have a major impact on the ingestive behavior of animals. Particularly well-documented are the feeding and drinking effects of JIB and vagotomy. These two surgical procedures are similar in that they reduce the food intake and body weight of obese animals more than that of lean animals, and of hypothalamic obese rats more than that of genetically obese rats. Intermediate effects are obtained with other obesity models. Given the multiple etiologies of human obesity, it is not surprising that gastrointestinal surgery has variable effects in obese humans. The effects of gastric surgery on the ingestive behavior of animals have received relatively little attention. This is unfortunate because gastric bypass is now one of the most widely used methods for surgical treatment of human obesity. In light of recent developments in gastric surgical techniques and new findings concerning the gastric modulation of food intake, the effects of gastric surgery on the feeding behavior of animals should be further investigated. Much remains to be learned about the physiologic and behavioral mechanisms by which gastrointestinal surgery influences ingestive behavior and body weight. Surgical manipulations of the gastrointestinal system may affect ingestive behavior by directly altering the neural and hormonal feedback signals to the brain from the stomach, intestines, and other organs (liver, pancreas), or they may indirectly alter these feedback signals by modifying the preabsorptive and/or postabsorptive flow of nutrients. Seen from a functional perspective, the gut sends to the brain different types of messages that modulate ingestive behavior. Most attention has focused on gut satiety signals, but the gut can also be the source of painful sensations that suppress ingestive behavior. The distinction between satiety and discomfort is not always clear-cut. For example, gut distention may be satiating when it is moderate, but painful when it is extreme. Nevertheless, the distinction is an important one, and the nature of the feeding-inhibitory effects obtained in animal studies must be carefully evaluated. Ideally, obesity surgery should produce minimal aversive consequences, although whether it is possible to reduce food intake and body weight without producing any discomfort remains to be established. In addition to being a source of feeding-inhibitory cues, the gastrointestinal system may also provide excitatory cues that stimulate feeding and modify food preferences. For example, intestinal infusions of carbohydrates increase subsequent food intake under certain conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Rats offered a carbohydrate solution (sugar or polysaccharide) in addition to chow typically overeat and gain excessive weight. The present study sought to determine if the palatable taste of these solutions contributes to the overeating response. Adult female rats were fitted with chronic intragastric catheters and given ad libitum access to chow and a drinking fluid that was paired with intragastric infusions. For one group (P + S), the flavored solution was a highly preferred mixture of 2% Polycose and 0.2% saccharin paired with intragastric infusions of 30% Polycose. For a second group (SOA), the flavored solution (0.03% sucrose octaacetate) had unpreferred bitter taste and was paired with intragastric infusions of 32% Polycose. Thus both groups were effectively exposed to the postingestive effects of 32% Polycose but paired with a palatable (P + S) or unpalatable (SOA) flavor. A control group had water to drink paired with intragastric water infusions. During the 4-wk experimental period, the P + S group consumed 34% more total energy (chow + Polycose) and gained more weight than did the SOA and control groups. The P + S group also consumed substantially more flavored solution and more energy as Polycose compared with the SOA group. The SOA group did not gain reliably more weight than the control group, although their total energy intake was 13% higher than that of the controls. In a choice test conducted at the end of the experiment, the P + S group displayed a strong preference (98%) for the Polycose + saccharin solution over water. In contrast to the control group, which avoided the SOA solution relative to water, the SOA group preferred the SOA solution (71%) confirming prior reports of Polycose-conditioned SOA preferences. These results demonstrate that palatability has a major effect on the overeating and obesity produced by carbohydrate solutions. In the absence of a highly preferred taste, the postingestive actions of Polycose produce only a small hyperphagic effect and no excess weight gain.

The role of postingestive factors in the preference for and overconsumption of high-fat (HF) foods, relative to high-carbohydrate (HC) foods, was investigated using a self-regulated intragastric feeding procedure. On one-bottle training days, rats drank one flavored saccharin solution [conditioned stimulus (CS) + HF] paired with intragastric infusions of an HF liquid diet, a second flavored solution (CS+HC) paired with an HC liquid diet, and a third flavored solution (CS−) paired with intragastric water. The diets had the same energy and protein content; the CS solutions and infusions along with chow were available ad libitum. The rats drank more CS and self-infused more diet on HF than HC training days. In two-bottle choice tests, the rats preferred the CS+HF to the CS+HC and both CS+HF and CS+HC to the CS−. The rats consumed more CS+HF than CS+HC by taking more bouts per day; bout sizes did not reliably differ. In a subsequent experiment, rats preferred the CS+HF even though diet intakes in training were matched. In a final experiment, the CS+HC and CS+HF intakes were equated in training by diluting the HC diet. Now the rats did not reliably prefer the CS+HF to the CS+HC, yet caloric intakes were much higher on CS+HF than CS+HC training days. Thus, relative to an isocaloric HC diet, the postingestive effects of HF diets stimulate overeating and condition a stronger flavor preference. Reduced satiety rather than increased reinforcement may be the direct promoter of overeating. However, postingestive reinforcement may enhance the selection of HF foods when a choice of HF and HC foods is available.

Rats were fitted with gastric cannulas, food deprived, and allowed to drink a sugar solution that drained out of the opened cannula; i.e., the rats sham-fed. Although this procedure is thought to prevent absorption of ingested food, it was found that the sham feeding of a 32% glucose or sucrose solution significantly elevated blood glucose levels. The addition of acarbose, a drug that inhibits the digestion of sucrose, to the 32% sucrose solution blocked the blood glucose rise, as did closing the pylorus with an inflatable pyloric cuff. Neither the drug nor the cuff, however, reduced the amount of sucrose solution consumed. These findings indicate that gastric sham feeding does not necessarily prevent the digestion and absorption of food, although absorption is not essential for the appearance of a vigorous sham-feeding response. Nevertheless the possibility that neural or hormonal feedback from the stomach contributes to the sham-feeding response cannot be excluded, and until this issue is resolved the results of gastric sham-feeding studies should be interpreted with caution.

An inexpensive low-power microscope is described for use in stereotaxic surgery. The microscope aids in the measurement of skull landmarks and improves the accuracy of stereotaxic surgery.