Liquid diet preference in weanling rats with dorsomedial hypothalamic lesions

Two groups of weanling rats received bilateral electrolytic lesions in the ventromedial and dorsomedial hypothalamic nuclei, respectively. Sham-operated animals served as controls. During 14 days post-operation, the intake of standard laboratory chow was measured. The rats then received, in addition to laboratory chow and tap water, a sweet, eggnog-type liquid diet for 17 days, during 14 of which food intake from both diets was measured daily. The liquid diet was then withdrawn and for two weeks laboratory chow was again the sole source of calories. During the availability of the liquid diet, both groups of rats with hypothalamic lesions profoundly reduced their intake of laboratory chow but conspicuously increased their consumption of liquid diet. The rats with dorsomedial lesions consumed as much liquid diet as the controls, while on laboratory chow alone they were highly significantly hypophagic compared with the controls. During the availability of the liquid diet the rats with dorsomedial lesions also became obese, but after the return to a period in which laboratory chow was the sole source of calories they lost this extra fat while again being hypophagic.It is suggested that the hypophagia observed in rats lesioned in the dorsomedial hypothalamic nucleus is not due to a deficiency in caloric metering but rather, alternatively, to (a) aversion to dry food, (b) taste preference for a sweet, liquid diet, (c) a motivational deficit or (d) a motor deficit.     

Effect of diet consistency, taste and calories on food intake of weanling rats with dorsomedial hypothalamic lesions

Male weanling Sprague-Dawley rats with dorsomedial hypothalamic lesions (DMNL rats) primarily destroying the dorosomedial hypothalamic nuclei (DMN) showed significant hypophagia on lab chow chunks compared to sham-operated controls. When given a choice between lab chow in the form of chunks or powder, both controls and DMNL rats ate similar amounts of lab chow powder while DMNL rats ate less lab chow chunks. Total caloric consumption was the same as on chunks alone. When returned to lab chow chunks as the only source of calories, the pattern and magnitude of intake was again depressed for the DMNL rats. When offered a choice between Ginger Snaps cookies in chunk form versus powder, DMNL rats remained hypophagic in terms of chunk consumption while the intake from powder was similar in both controls and DMNL rats. When offered a choice between chunks of lab chow and Ginger Snaps, DMNL rats were again hypophagic on lab chow chunks, ate the same as the controls of the cookies, and the total caloric intake was of the same magnitude and pattern as observed in previous tests. The data suggest, but do not conclusively show, that DMNL rats are not hypophagic because they have an aversion to chewing hard food and that, when offered a diet similar in hardness to lab chow chunks i.e., hard cookies, will prefer the less tasty but nutritionally complete lab chow. They are apparently capable of choosing a diet for complete nutrition and, as previously reported, can meter calories competently.     

Somatic and metabolic responses of mature female rats with dietary obesity to dorsomedial hypothalamic lesions: Effects of diet palatability

Caloric intake, body weight, obesity status (Lee Index) and incorporation of U-14 C-glucose into liver and retroperitoneal fat pad glycogen and lipid were studied in mature female rats that had received bilateral lesions or sham-operations in the dorsomedial hypothalamic nuclei (DMN) after dietary obesity was well established. Their diet consisted of a high-fat-sucrose chow mix, chocolate chip cookies and a drinking fluid of 32% sucrose in tap water. Comparable groups of DMN lesioned rats (DMNL rats) and sham-operated controls were maintained on lab chow pellets and tap water. Prior to the hypothalamic operation, the animals on the high-caloric regimen consumed significantly more calories than the rats on lab chow and also attained commensurately higher body weights and obesity indices. The bulk of the calories consumed during this time was derived from the cookies. Following DMNL, the animals maintained on lab chow became hypophagic and had lower body weights than the sham-operated rats, as has been previously reported. In rats on the high-caloric regimen, DMNL resulted in hyperphagia in comparison to all other groups. The greatest percentage of the calories during this time was derived from the high-fat-sucrose chow mix and sugar water. Correspondingly, DMNL rats on the high-caloric regimen had higher body weights and obesity indices than all other groups. At sacrifice, both a diet and lesion effect were noted in an elevated incorporation of U 14-C glucose in both fat pad and liver lipid and glycogen. The data are interpreted to mean that (1) when a highly palatable, high-caloric diet is available, DMNL do not exert their usual hypophagic and weight-lowering effects; (2) DMNL and control rats show excessive caloric intake when both groups are fed a highly palatable, high-caloric diet in comparison to their chow-fed counterparts. However, DMNL rats fed high-caloric diet also consume significantly more than controls fed this diet; (3) This excessive caloric intake of the DMNL rats possibly predisposes these animals to exaggerated lipogenesis in liver and adipose tissue; (4) the sham-operated controls on the high-caloric regimen also show greater lipogenesis but at a level intermediate between the chow-fed controls and the DMNL rats on the high-caloric diet.     

Meal patterns of rats with dorsomedial hypothalamic nuclei lesions or sham operations

Rats with bilateral dorsomedial hypothalamic electrolytic lesions (DMNL rats) are hypophagic, hypodipsic and have reduced linear and ponderal growth when compared to sham operated controls (SCON). Nevertheless, previous studies have shown that DMNL rats eat and drink adequate amounts for their size and have normal body composition. In the present study we investigated meal parameters: meal size, and frequency (both light and dark period), total intake and meal size per metabolic size (body weight 0.75). Compared to SCON, DMNL rats at twelve days post surgery weighed less, were shorter, but had a normal body composition as determined by the Lee Index, and were hypophagic (grams eaten/day). The animals were placed into individual, self-contained feeding modules and given powdered chow. After familiarization to the modules, meal parameters were recorded continuously by a computer for an eight day period. While dark phase meal frequency did not differ significantly between groups, the lesioned rats took more meals during the light period. Over the eight-day measurement period DMNL rats were hypophagic compared to SCON in absolute terms. However, when total intake and meal size were normalized to metabolic size, these two parameters did not differ significantly between groups. Upon refeeding, after a one-day fast, the initial meal size of the normally hypophagic DMNL rats exceeded that of SCON. Rats with DMNL have previously been shown to have deficits in some hypothesized short-term food intake control mechanism (e.g., cholecystokinin, glucose sensing). Thus overeating by the lesioned rats after a fast could possibly result from a specific short term control deficit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rats drinking quinine- or caffeine-adulterated water defend lean body weights against caloric and osmotic stress

Adult male and female rats drank ad lib water containing as much as 0.2% quinine hydrochloride or caffeine, and ate dry food. Maintained body weights were lower in direct proportion to the concentration of adulterant. Cumulative caloric intakes and the water and fat contents of carcasses showed that the weight lost on adulterated water and regained on tap water was fat rather than fluid. Furthermore, lean rats on adulterated water ate and drank more when ambient temperature was reduced; drank more and approximately maintained caloric intake when their food contained up to 5% sodium chloride; and ate less to compensate for the caloric value of a nonhydrating liquid diet force fed by gavage. The rats also adapted to activity wheels and behaved like rats drinking tap water during and after two days of food deprivation. Thus, the percentage adulteration of obligate drinking water determines the body weights at which rats eat and drink to defend energy balance. The rats remain in water balance even though ratios of water to food intakes were depressed by one-third in males and one-half in females for concentrations of adulterant between 0.05 and 0.2%, inclusive. These results can be used to argue that standard concepts and procedures for describing motivational and physiological states are inadequate.     

Parametric study of the regulatory capabilities of rats with rostromedial zona incerta lesions: Responsiveness to hypertonic saline and polyethylene glycol

Rats with lesions in the dorsomedial zona incerta (ZI): (1) were hypodipsic; (2) drank little or nothing during periods of food deprivation; (3) drank little or nothing after injections of 5 ml of 0.50 M, 0.75 M, 1.0 M or 2.0 M NaCl solutions (some animals displayed delayed responses to the highest dose, 6 and 24 hr after the injection); (4) drank normal quantities of water or saline after 5 ml of 15%, 20%, or 30% PG (half of the animals that had shown absent or severely impaired responses to hypertonic saline; the other half did not drink saline or water in response to any dose of PG except the highest—5 ml of 30%); (5) sharply reduced or abolished sodium appetite; (6) reduced or abolished the feeding response to 2-DG without affecting ad lib food intake. Similar effects on 2-DG eating and sodium appetite (but not on water intake under ad lib or food-deprivation conditions, or on drinking in response to hypertonic saline or PG) were produced by lesions in ventral thalamus or dorsomedial hypothalamus.     

The regulation of feeding and drinking in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate.

Rats bearing excitotoxic lesions of the lateral hypothalamus are hypodipsic and hypophagic, but responses to 24 h food or water deprivation are normal, as are responses to different taste stimuli. The most striking deficit present in lateral hypothalamic-lesioned rats is an inability to respond as controls to dehydrating, dipsogenic or glucoprivic challenges. The present experiments examined the ability of rats bearing bilateral N-methyl-D-aspartate-induced lesions of the lateral hypothalamus to recognize and respond to changes in their internal environments. All of the lesioned rats tested showed mild to moderate hypophagia and hypodipsia, and none responded properly by drinking over 1 h after i.p. injection of hypertonic saline. However, the addition of glucose to the water supply promoted an increase in drinking and a decrease in lab chow consumption to maintain a constant energy intake; the addition of salt to the diet promoted an increase in drinking and no change in eating; 24 h water deprivation induced the same amount of drinking in lateral hypothalamic-lesioned rats as in controls; and injection i.p. of water (but not physiological saline) before drinking water was returned to rats which were 24 h water deprived suppressed drinking. These data suggest that lateral hypothalamic-lesioned rats are in receipt of normal information from their peripheries, and that they can adjust their behaviour over a period of days or minutes to changes in the internal milieu. The most consistent deficit is in responding actively and rapidly to challenging stimuli; the nature of this and the mechanisms which might produce it are discussed. We suggest that the consequences of excitotoxic lesion are better explained by disruption of input to the cortex from the lateral hypothalamus rather than by interference with metabolic processes.     

Delayed acquisition of schedule-induced polydipsia in rats with zona incerta lesions

Rats with lesions of the zona incerta (ZI) were hypodipsic under free-feeding conditions and were adipsic during periods of food deprivation. Lesioned rats did not differ from controls in daily food intake. In schedule-induced polydipsia (SIP) tests conducted by reducing the rats to 80% of free-feeding body weight and delivering 45 mg Noyes pellets on a fixed-time 1-min schedule, ZI lesions significantly delayed the acquisition of SIP. Both the size and frequency of post pellet drinking bouts were affected by the lesions. After 26 SIP sessions lesioned rats were drinking at levels similar to controls.     

Effects of VMH lesions on schedule induced and schedule dependent behaviors

Ten male hooded rats were exposed to an FI 1 min food reinforcement generator schedule at 80% body weight and schedule dependent lever pressing and schedule induced licking and drinking were recorded. When lever pressing, licking, and drinking stabilized the 10 rats were divided into two groups. One group was composed of 4 animals subjected to sham lesion procedures plus one animal with asymmetrical ventromedial hypothalamic (VMH) lesions. The other group was composed of 5 animals with bilateral symmetrical VMH destruction. Results demonstrate that VMH destruction produces a slight transient decrease only in water intake when on schedule at 80% body weight. When animals are returned to ad lib eating and body weight increased and they are returned to the test chamber, the VMH lesion animals display increased licking and drinking. Although VMH lesion animals ate and drank more than controls, they did not eat more in response to food deprivation and did not drink more in response to water deprivation and the intraperitoneal administration of hypertonic saline. The presence or absence of food or water was the determining factor in the overeating or excessive drinking of the VMH lesion animals. Results are discussed in terms of gastrointestinal influences on the hypothalamic mechanisms involved in the production of schedule induced behaviors.     

Nocturnal food-related hyperdipsia in the adult spontaneously hypertensive rat

Male adult spontaneously hypertensive rats (SHR) ate the same but drank more and had a higher water to food ratio (W:F) than did Wistar-Kyoto (WKY) rats in 24-hr when they had continuous access to standard laboratory pellets and tap water. When rats ate in the day phase of a 12:12 light/dark cycle after 24-hr food deprivation, SHR rats ate and drank the same as did WKY rats in a 60-min test. When the same rats ate at night after 24-hr food deprivation, however, SHR rats were hyperdipsic: They ate the same as did WKY rats, but SHR rats drank more and had a higher W:F. This relative hyperdipsia reflected the increased ability of ingestion of food to stimulate drinking in SHR, because when food was absent for a 60-min test at night SHR drank the same as did WKY rats. Three dipsogens which are candidate components for eating-elicited drinking in the rat, cellular dehydration, histamine and angiotensin II, elicited drinking differentially in SHR and WKY rats: SHR drank more than did WKY rats in response to (1) cellular dehydration produced by IP hypertonic saline, (2) large doses of SC histamine, and (3) SC angiotensin II. These results demonstrate that SHR exhibit a nocturnal food-related hyperdipsia which may reflect differential sensitivity to stimuli important for eating-elicited drinking such as increased osmolality and endogenous histamine or angiotensin.     

Meal-induced decreases in serum corticosterone in the lateral hypothalamic syndrome

Decreases in serum corticosterone levels were used to quantify positive emotional responses to meals in rats that survived bilateral lateral hypothalamic lesions (n=9), intraventricular 6-hydroxydopamine injections with pargyline pretreatment (n=3), or without it (n=8) and operated controls that were fed either ad lib (n=19) or were pair-fed with brain-damaged rats throughout the study (n=11). Meals of dry powdered chow and tap water, offered in the evening after 8 hr of food and water deprivation, did not reliably reduce corticosterone levels within 30 min. When the rats were forced to eat their entire daily food ration during a 1-hr morning period for over 2 weeks, corticosterone levels were lower within 10 min of meal onset than they were prior to feeding. Placement of the rats into chambers in which they had received their daily meals was also effective in reducing corticosterone levels. Lateral hypothalamic or 6-hydroxydopamine lesions did not affect the magnitude of the corticosterone decreases, but did affect changes in glucose levels associated with meals. The data were discussed in terms of mechanisms involved in the permanent hypophagia of the lateral hypothalamic syndrome.     

On the motivational deficits after medial hypothalamic lesions

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

Feeding studies in weanling rats with dorsomedial hypothalamic lesions: maintenance of competence to compensate for additional calories.

Weanling rats received bilateral electrolytic lesions in the dorsomedial hypothalamus primarily destroying the dorsomedial hypothalamic nuclei (DMN). Sham-operated rats served as controls. After a 14 day postoperative period during which food intake (lab chow) and body weight were recorded, each of the above groups were subdivided into 2 groups. One DMN group and one sham-operated control group were continued on lab chow alone throughout the remainder of the study. The other DMN group and the second control group were given additional calories in the form of a liquid diet by stomach tube during 2 separate periods of 10 and 14 days, respectivly, to increase their caloric intake beyond that taken in spontaneously. Both tube-fed groups reduced their ad lib caloric intake from chow considerably and to the same extent. Body weight gains were similar in tube-fed versus non-tube-fed rats, whether with or without DMN lesions. After the second, 14-day-long tube feeding period, however, DMN rats regulated their body weight somewhat less precisely than the controls. This may be related to their reduced food intake during that time period. The data indicate that weanling rats with DMN lesions, despite their basic hypophagia, do not show a deficit in caloric metering and gross body weight regulation.     

Saliva hypersecretion during aphagia following lateral hypothalamic lesions

Using a new and simple technique, saliva output was measured in rats with lesions in the lateral hypothalamic area (LH). While aphagic and adipsic during the first several days after surgery, the LH rats showed a dramatic hypersecretion of saliva relative to control rats subjected to sham operations and food and water deprivation. In contrast, rats recovered from aphagia for several months showed a hyposecretion of seliva, both in room temperature and in a hot environment. The results are discussed as they relate to the emphasis on autonomic consequences of LH lesions.     

Hunger, thirst and their interactive effects on the rat's drinking in a saccharin-water choice

In a 3 × 3 factorial in which hours of food and water deprivation were varied, Sprague-Dawley rats preferred water to 1.0% saccharin and drank large volumes of it providing hours of water deprivation (thirst), exceeded hours of food deprivation (hunger). All other, i.e. undeprived, equally hungry and thirsty rats, and those whose hunger exceeded thirst preferred 1.0% saccharin but drank small amounts relative to the amounts of water drunk by the thirsty rats. The combined results of this and previous studies employing both choice and single-tube conditions, suggested that thirsty rats drink saccharin primarily for water and to a lesser extent and only with experience, for the sensory stimulation which saccharin provides. Hungry rats drink it primarily for the sensory stimulation. Saccharin in a choice with water seems to provide a means for the determination of the momentarily dominant drive state in naive rats.     

Ingestive behavior in adult rats with dorsomedial hypothalamic lesions

Large lesions in the dorsomedial hypothalamus (DMH) resulted in transient hypophagia that produced a significant weight loss. Energy intake per g of body weight returned to normal levels within 2 weeks after surgery but the body weight loss incurred during the immediate postoperative period was not compensated in 3 months of observation. The experimental animals responded poorly, if at all, to 2-deoxy-D-glucose induced cellular glucoprivation but ate normally after 2 doses of insulin and compensated appropriately for 24 hours of food deprivation. Rats with DMH lesions also displayed persisting hypodipsia (even when the animals' reduced body weights were taken into account) but responded normally, or nearly so, to water deprivation (with and without food), cellular dehydration, or extracellular hypovolemia. (Rats with DMH lesions drank slightly less than controls on most of these tests even when their chronically lowered body weights were taken into account but the impairment was small and, in most instances, not statistically reliable.)     

Accumbens cholinergic interneurons play a role in the regulation of body weight and metabolism

The aims of the present study were (1) to determine whether selective lesions of the accumbens cholinergic interneurons impair feeding and body weight regulation, and (2) to characterize the nature of disturbances using motivational and metabolic challenges. Rats with bilateral cholinotoxic (AF64A) lesions in the nucleus accumbens showed a significant and lasting lag in body weight gain in comparison to the sham-operated controls. This failure to gain weight was not due to a decrease in feeding because lesioned rats actually ate more food and drank more water than controls under basal conditions. Lesion-induced deficits were also exposed when the rats were challenged with food deprivation or cold exposure. Lesioned rats ate less than controls when 24 h food deprived and maintained both a higher core temperature and a higher metabolic rate than controls following either 24-h food deprivation or exposure to cold. Thyroid hormones, insulin, and blood glucose levels were, however, within the physiological range, and no sensory and motor disturbances were observed. The results suggest that the altered body weight regulation is partly due to the enhanced metabolic responsiveness to stress. Possible explanations for the effects of the lesions are also discussed in the context of motivational alterations, including possible dopamine-acetylcholine interactions.     

NMDA lesions of lateral hypothalamus enhance the acquisition of schedule-induced polydipsia.

Schedule-induced polydipsia (SIP) is affected by damage to various limbic structures that have connections with the lateral hypothalamus. The present experiment sought to determine whether or not SIP could be induced in rats bearing NMDA-induced lesions of the lateral hypothalamus. Following surgery, lesioned rats lost weight and were hypophagic and hypodipsic. Drinking, in response to systemic injection of hypertonic saline, was impaired in lesioned rats. Prior to testing for SIP, all rats were placed on a food-restriction regime to maintain body weight at 85% of normal. There was no statistically significant difference in mean body weight between lesioned and control groups before deprivation began, though lesioned rats were hypodipsic in their home cages. The lateral hypothalamic-lesioned rats acquired SIP significantly more rapidly than controls over the first six sessions, but over four following sessions no differences were present. The enhanced acquisition of SIP by lateral hypothalamic-lesioned rats cannot be accounted for by postoperative recovery of body weight or by hypodipsia in the home cage, neither of which correlated with SIP. It is suggested that the lateral hypothalamus has a role in cueing appropriate and inhibiting inappropriate behavior in conditions of motivational excitement. SIP is suggested to have two CNS components--one excitatory and one inhibitory.     

Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats

Radiofrequency heat lesions were made in the medial hypothalamus of 12-week old male and female Holtzman rats. Two to three days later rats were offered a palatable cafeteria diet in addition to chow or were fed chow alone for the next 3-4 weeks. Male lesioned rats were only slightly hyperphagic on the chow diet and gained little extra weight. When fed the cafeteria diet, energy intake of male lesioned rats almost doubled in comparison with chow-fed lesioned rats and a very rapid extra weight gain occurred. Despite the marked hyperphagia, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed lesioned rats, as indicated by low mitochondrial guanosine diphosphate (GDP) binding. In female rats, lesions induced much greater hyperphagia and body weight gain than in male rats, particularly when they ate the cafeteria diet. Again, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed female lesioned rats. The proportion of energy derived from carbohydrate was not altered by the cafeteria diet in either male or female rats, whether lesioned or not, but there was an increase in the proportion of energy derived from fat at the expense of protein. No sex differences in food selection were observed. The accumulation of body fat was always greater in female lesioned rats than in male lesioned rats for similar food intakes. It is concluded that medial hypothalamic lesions prevent the normal occurrence of diet-induced thermogenesis in brown adipose tissue despite extreme overeating by the rats of a palatable cafeteria diet.     

Competitive behavior: intact male rats but not hyperdefensive males with medial hypothalamic lesions share water with females

Male hooded rats with medial hypothalamic lesions or sham lesions were given tests of defensiveness toward an experimenter. The 8 lesioned males with the highest defensiveness scores and 7 sham-lesioned males were each placed in a double cage with a single intact female. For each pair of rats, food was continuously present but water was available for only 1 hr/day through a single water spout. Beginning on the fifth day of water deprivation, each pair of animals was given a 4-min water competition test on 3 consecutive days. Competition for water was created by placing a plastic ring over the hole in the cage where the water spout entered the cage. The ring restricted access to the spout to a single animal and was put in place 5 min before water was given. One hr following the competition test, each pair of animals was given access to a single unencumbered spout for a 1-hr period. Rats with medial hypothalamic lesions drank significantly more and initiated more aggression than their female cagemates during the 4-min competition tests. Sham-lesioned rats neither drank significantly more nor were more aggressive than their female cagemates. These results are consistent with previous observations indicating that the aggressiveness of rats with medial hypothalamic lesions can be elicited by a competition situation.