Role of gonadal hormones in diet selection and food utilization in female rats

Patterns of dietary self-selection were examined in ovariectomized and sham-operated female rats. Self-selection animals were offered separate dietary sources of protein, carbohydrate, and fat. Control animals were offered ground Purina Rodent Chow. Food intakes, water intakes, and body weights were measured daily for all animals. During a 19-day baseline period, selecting animals chose approximately one third of their daily caloric intake from each of the three diet sources. Following this baseline period, half of the self-selection animals and half of the control animals received bilateral ovariectomies, while the remaining animals in each diet group received sham-operations. Following ovariectomies, both self-selection and control animals significantly increased food intakes and rate of weight gains above baseline values. In contrast, sham-operated animals did not increase food intakes or rate of weight gain following surgery. When weight gain was calculated as a function of caloric intake, ovariectomized animals gained nearly twice as much weight per kilocalorie consumed as sham-operated animals. Ovariectomized animals showed no changes in diet selection after surgery, while sham-operated animals showed a slight decrease in the percentage protein selected. Differences between self-selection patterns in ovariectomized animals and in animals with other forms of experimentally-induced obesity suggest distinct metabolic patterns may underlie various forms of obesity.     

Endocrine and metabolic regulation of body mass by nicotine: role of growth hormone

This study was conducted in male Sprague Dawley rats, maintained chronically on drinking water and on nicotine water at nicotine concentrations of 0.31 and 1.23 mM, to determine the effect of nicotine on body weight regulation and circulating growth hormone levels. The study was repeated to determine the effect of nicotine withdrawal on the same parameters after exposing the animals to high dose of nicotine (1.23 mM) for 12 weeks and then removing the nicotine from water for four weeks. Growth hormone (GH) and insulin levels in the plasma were measured by sensitive radioimmunoassays. The results show that with nicotine treatment the body weight, food and fluid intakes in rats decreased significantly, concomitant with the decrease in plasma glucose and insulin levels while plasma growth hormone levels were increased significantly. A pair-fed study conducted to determine the effect of decreased food intake showed no alteration of metabolic or hormonal parameters. Withdrawal of nicotine for four weeks reversed all of the previously noted parameters including plasma growth hormone levels; however, the body weights were not completely reversed. The data suggest that intake of nicotine affects body weights which appear to be associated with decreased plasma levels of glucose and insulin and release of growth hormone may play a role in that mechanism.     

Effects of chronic administration of naloxone on wheel running activity in rats under 2-h feeding schedule

The effects of chronic administration of naloxone (120-150 micrograms X kg-1 X h-1) on the wheel running activity (WR) and on food and water intakes were studied in male Wistar rats subjected to a 2-h restricted feeding (1200-1400 h) schedule at 24 +/- 1 degrees C and LD 12:12 (L: 0600-1800 h) cycle. The restricted feeding significantly increased WR before and after the feeding time. Food and water intakes per day were reduced and body weight gradually decreased for the 2-week food restriction period. Food and water intakes appeared to be suppressed by naloxone, particularly shortly after the administration. The chronically administered naloxone slightly increased the 24-h WR. In the naloxone-treated rats, the fraction of WR before the feeding time (anticipatory activity) was significantly increased compared with saline-treated rats. The fraction of WR after the feeding time (succeeding activity) did not change. These results suggest that the endogenous opioid system may play a role in suppressing the excess increase in the anticipatory locomotor activity in the food restricted rats.     

Area postrema/nucleus of the solitary tract ablations: Analysis of the effects of hypophagia

The effect of hypophagia following lesions of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) on body-weight, water intake and preference for palatable diets was examined. Following AP/cmNTS ablation, rats reduced pelleted-food intake to a degree which was sufficient to account for the weight loss and increased water:food ratios observed. Restricting food intakes of intact rats to levels taken by lesioned animals resulted in similar weight losses and increased water:food ratios. When offered both pelleted food and milk, lesioned rats took more calories as milk than did previously food-restricted intact rats. Thus, the hypophagia of AP/cmNTS lesioned rats does not account for their increased preference for milk diets. Lesioned rats ate less high-fat diet than did intact or sham-lesioned controls and did not increase their intakes when this diet was sweetened. At autopsy, retroperitoneal and epididymal fat-pad weights accounted for less of the total body weight of lesioned animals than controls suggesting that body-fat levels are reduced following AP/cmNTS ablation.     

Weight loss following LH lesions independent of changes in motor activity or metabolic rate

Lesions in the lateral hypothalamus (LH) which resulted in aphagia and a significant loss in body weight, did not reduce either the running wheel activity or the stabilimeter activity of the animals. Following recovery, the animals failed to regain the lost weight. They had normal food and water intakes under ad lib conditions, and ate food when water deprived. They did not drink when deprived of food. Both control and LH animals also had higher than normal oxygen consumption rates. However, the LH group was not higher than the controls postoperatively. These data argue against their being a unitary LH lesion syndrome and suggest that the chronic weight loss seen in animals with LH lesions is not a secondary consequence either of having disrupted the pituitary-thyroid axis, or of having changed the animals' spontaneous activity levels.     

Effects of chronic quinine-adulteration of the water supply on food and fluid intake and body weight in lean and obese hypothalamic hyperphagic rats.

Obese rats with lesions of the ventromedial hypothamamus (VMH) consumed little or no food or fluid for 8–20 days when their water supply was chronically adulterated with 0.03% quinine hydrochloride. Three of the obese animals consumed significant amounts of food and fluid after the first week, five others continued to lose weight (at the rate of approx. 10 g./day) throughout the experiment. The experiment was terminated after 20 days when two animals died, and three others were so emaciated that death appeared imminent. Lean VMH rats that had been maintained at pre-operative body weights by restricted feeding prior to the quinine adulteration reduced their liquid and food intake only briefly after the quinine was introduced. After 4 or 5 days these animals were hyperphagic and hyperdipsic and displayed a substantial and sustained increase in body weight during the remaining 15 days of the experiment. The control animals curtailed both food and fluid intake sharply during the first 24–48 hours after the introduction of the quinine adulteration. Fluid intake subsequently recovered to approx. 60% of baseline and food intake returned to essentially normal levels. Body weight remained stable although slightly below baseline throughout the 20-day test period. The different response to quinine-adulterated water by lean and obese VMH-lesioned rats is similar to previously reported reactions to adulterated food. It is therefore concluded that explanations of VMH finickiness in terms of dysfunctions in appetite or hunger (terms appropriate only for food intake) are too limited. A more general deficit is proposed.     

Weight loss,slower growth and lower fasting heat production rates following LH lesions in female rats

Lesions in the lateral hypothalamus (LH) can result in a permanent loss of body weight and slower growth in female rats, but do not do so invariably. Weight and growth rate changes were always accompanied by lower rates of fasting heat production (FHP) independent of changes in activity. The thyroids of these animals were significantly below normal in size. None of the traditional deficits of the “LH syndrome” were present: the animals ate when deprived of water: drank when deprived of food (although less than the control animals) and increased their food intakes when injected systemically with insulin, at least on the initial test. With repeated tests the food intake following insulin-induced hypoglycemia declined both in the animals with lesions and in the animals whose body compositions and weights had been lowered to the same levels.     

Preoptic hypernatremic syndrome and the regulation of water balance in the rat

Lesions of the medial preoptic area in rats cause a transient adipsia and aphagia, with a weight loss of 15–20%. Feeding and drinking behaviours return, with water intakes similar to sham-operated rats. However, the rats remain chronically hypernatremic for a period of at least 2 months. The hypernatremia persists during food deprivation and during stimulation of drinking by extracellular dehydration. No deficiency is evident in urinary concentrating ability or in ability to excrete sodium ions; extrarenal water loss is similar to that of sham-operated rats. The rats do not drink in response to hypertonic saline injection, and they do not retain an imposed water load. A comparison with rats with diabetes insipidus, which avoid hypernatremia by sharply increasing their water intakes, demonstrates that the hypernatremia is related to a dysfunction of intake as well as output. The findings suggest that medial preoptic lesions may reset the set-point for regulation of plasma sodium concentration; they also suggest that the lesions may cause reduced sensitivity to an increase in plasma sodium concentration.     

Behavioral and electrophysiological changes following microinjections of colchicine into the substantia nigra.

Male Sprague-Dawley rats received bilateral microinjections of colchicine (2 or 4 μg in 1 μl) into the substantia nigra. During the first 2 days the animals were hyperactive, intense gnawing and chewing were observed, and food intake was significantly increased. During the next 3 or 4 days, activity, food and water intakes and body weight gain were markedly reduced; the behavior was similar to that previously observed following damage to the substantia nigra and nigrostriatal pathway from 6-hydroxydopamine or electrolytic lesions. This period of hypophagia and hypodipsia was followed by a rebound increase in food and water intake for several days until body weight returned to normal levels. Field potentials recorded from the caudate nucleus in response to electrical stimulation of the substantia nigra were reduced in amplitude during the first 4 days following microinjections of colchicine into the substantia nigra and recovered by Day 7.These reversible behavioral effects of microinjections of colchicine into the substantia nigra confirm the importance of the nigrostriatal pathway in motor and ingestive behaviors.     

Food intake and utilization in lateral hypothalamically lesioned rats

The daily food intake of rats with lateral hypothalamic (LH) lesions was monitored in two experiments. Confirming earlier reports, LH-lesioned animals were found to ingest nearly the same amount of food per day as nonlesioned controls even though their body weights remained substantially below those of the controls. In view of this result, an experiment was conducted to compare the efficiency of food utilization of LH-lesioned and control animals at different body weights. First, the daily food intakes of seven LH-lesioned rats and seven nonlesioned controls were determined. The body weights of these animals were then lowered by restricting food intake in four successive weekly periods to 85%, 70%, 55% and 40% of their ad lib level. Finally, all animals were refed for one week at their prerestriction levels of food intake reduced in proportion to the intervening loss in metabolic mass (body weight_kg^0.75). At each level of caloric restriction, the weight losses observed in the LH-lesioned and control animals were equivalent. Likewise, though given only prerestriction amounts (indexed to their reduced metabolic mass), LH-lesioned and nonlesioned animals both gained weight rapidly and at equivalent rates during refeeding. Thus, LH-lesioned animals appear to utilize food in a normal fashion and, as do controls, adapt to weight loss by increasing their efficiency of food utilizazion. In the case of LH-lesioned animals, however, such adjustments occur around a reduced level of maintained body weight, or set-point.     

The effects of liver denervation on food and water intake in the rat

In Experiment 1, liver denervations or sham operations were performed on rats in two separate trials. Food and water intakes and body weights of denervated rats did not deviate significantly from their sham operated controls. Male and female rats responded similarly. In Experiment 2, in addition to daily food and water intakes, initial daily meal size was investigated in two groups of liver denervated and sham operated rats. Initial daily meal size was determined during a one hour test at the start of the dark period of the light:dark cycle. In one group of rats a chow diet was used for testing, while a liquid diet was utilized in the second group. According to the “liver glucoreceptor preabsorptive satiety and general food intake control hypothesis” the denervated rats should have experienced a depression of daily food intake and preabsorptive satiety. No differences were found in either preabsorptive satiety or daily food and water intakes and body weights when denervated rats were compared to sham operated control animals. The results question whether liver glucoreceptors have any detectable influence on the control of feeding behavior. Certainly the data does not support the role of liver glucoreceptors as a major controller of feeding behavior in the rat.     

The nature of the thirst stimulus: a factor in conditioned taste-aversion behavior.

Independent groups of rats were compared drinking in response to either water deprivation or osmotic thirst induced by intraperitoneal injections of hypertonic saline. When water or a palatable saccharin solution served as the drinking fluid, deprivation and osmotic thirst produced comparable fluid intakes. In contrast, when a saccharin solution previously associated with the aversive effects of lithium served as the drinking fluid, animals injected with hypertonic saline drank substantially less than water deprived animals. Experiment 2 indicated that this hyperreactivity to a conditioned aversive flavor in animals suffering from osmotic thirst was due to the reduced palatability of the saccharin flavor rather than the previous experience with lithium. Experiment 3 showed that the effect also could not be attributed to differential taste-aversion learning, handling, food deprivation or weight loss before the test sessions. The phenomenon is discussed in terms of various differences between thirst induced by water deprivation and thirst induced by acute cellular dehydration.     

Effect of 5-thio-D-glucose on food and water intakes and on the acquisition and performance of maze tasks in the rat

A potent inhibitor of D-glucose transport across the membrane, 5-thio-D-glucose (5-TDG) was examined with respect to its effect on runway and maze performance as well as on food and water intakes and body weight. In an initial experiemnt, three groups of Sprague-Dawley rats were matched in terms of their performance to learn a runway taks with Noyes pellets serving as the reinforcement. After extinction, two groups of rats were given 5-TDG in their food for 14 days, in doses of 20 and 100 mg/kg/day, which exerts potent effects on other functions. Retesting in the runway task showed no significant differences in the time required for the controls and for the 5-TDG treated rats to reach the goal box. Nonfed controls and the same two groups were again fed 500 ant 100 mg/kg/day 5-TDG and were tested on the 12 problems of the Hebb-Williams maze. Again, no significant differences were found in the number of erros made on the 12 problems by the 5-TDG treated animals or by the controls. Thus, this sugar analogue, administered in doses that affect spermatogenesis and other processes, has no effect on the ability of the rats to perform these tasks. Similarly, the intakes of food and water were unaffected by the systemic administration of 5-TDG.     

Decreased food intakes and body weights in rats immunized against pancreatic glucagon

Glucagon, a putative satiety peptide, has decreased food intake and antibodies to glucagon have increased food intake when administered acutely. It may be hypothesized if rats were immunized against glucagon, antibodies would chronically sequester glucagon released during meals and food intake and weight gain would increase. Female Zucker obese (n = 16, BW = 160 +/- 5 g) and lean (n = 16, BW = 123 +/- 3 g) rats were immunized against pancreatic glucagon conjugated to BSA (GG-AB) or BSA alone (BSA-AB). Only GG-AB rats developed glucagon antibody titers (p less than 0.01). During a 16 week period average daily food intakes and body weight gains were decreased 5.0 (p less than 0.001) and 9.4% (p less than 0.001) respectively in GG-AB compared with BSA-AB rats. Free glucagon, measured by RIA using a pancreatic glucagon specific antibody, was decreased 60% at 8 weeks (130 vs. 322 pg/ml, p less than 0.001) and 33% at 16 weeks (206 vs. 307 pg/ml, p less than 0.02). However, total pancreatic glucagon (free and antibody-bound) was increased 226% (428 vs. 129 pg/ml, p less than 0.02) at 16 weeks. Thus, although sufficient antibody titers were developed in rats to sequester 76% of the free circulating glucagon from both pancreatic and gut sources, food intakes and body weight gains were decreased, likely as a consequence of an over-compensatory increase in total glucagon concentrations.     

Strain differences in drinking in inbred mice during ad libitum feeding and food deprivation

Water intakes were measured in 7 mouse strains under 3 conditions of food availability: (a) ad lib feeding, (b) $\text{1}\text{3}\text{-}\text{normal}$ food intake, and (c) total food deprivation. Under ad lib feeding strains were ranked according to magnitude of water intake. These ranks were similar, but not identical, when absolute water intakes (ml) and relative (ml/100 g body wt) water intakes were measured. Statistically reliable, positive correlations were found between food intake and body weight, water intake and food intake, and water intake and body weight. Under the $\text{1}\text{3}\text{-}\text{food}$ condition, mean water intakes decreased significantly from ad lib feeding conditions in the BALB/cJ, A/J and C57BL/6J strains, did not change significantly in the SWR/J, CBA/J and DBA/2J strains and increased (food-deprivation polydipsia) in the C3H/HeJ strains. Results in 2 replications of total food deprivation parallelled those of $\text{1}\text{3}$ normal intake except that in the former condition DBA/2J mice showed a significant decrease in water intake. Food-deprivation polydipsia was seen in some individual SWR/J and CBA/J mice, as well as in the C3H/HeJ strain but was very rare in the other four strains.     

Effects of electroconvulsive shock on food and water intake in the rat

Forty-two male rats were habituated to laboratory conditions for four weeks under constant light conditions. Food and water intakes were recorded daily. Following the habituation period half of the animals were given electroconvulsive shock (ECS) and half Sham-ECS (SECS). ECS treatments produced significant decrements in both food and eater intakes which returned to baseline levels after three days.     

Seasonal weight gain is attenuated in food-restricted ground squirrels with lesions of the suprachiasmatic nuclei

The role of seasonal hyperphagia in the genesis of prehibernation fattening was assessed in golden-mantled ground squirrels. One group of animals was fed ad lib throughout the weight gain phase of the annual body weight cycle (June-October); a group of neurologically intact animals and one of squirrels with brain lesions incorporating the suprachiasmatic nuclei (SCN) were fed amounts of food equivalent to quantities consumed prior to the body weight trough (May). Part of the seasonal increase of body mass is independent of increases in food consumption; intact animals fed ad lib or restricted to prefattening food intakes underwent similar increases in body mass and possessed equivalent amounts of abdominal white adipose tissue. Food restriction combined with SCN lesions attenuated seasonal weight gain and reduced abdominal fat mass. However, some of the brain-damaged squirrels still evidenced weight gain, a result supporting a previous conclusion that the SCN are involved in circannual body weight rhythm generation but their contribution to this process is not essential for continued rhythmicity in most individuals.     

Effects of glucose and saccharine solutions on subsequent food consumption

Twenty three hr water deprived animals were given access to various glucose and glucose + saccharin solutions during a 1 hr drinking session. Subsequent 1 hr and 22 hr food intakes were measured. Results indicate that more food was consumed during the first post drinking hour by the animals when receiving 3.5% GLU + 0.25% SACC while comparatively less food was consumed by them following the ingestion of 21% GLU and 21% GLU + 0.25% SACC. During the remaining 22 hr when the animals received 21% GLU and 21% GLU + 0.25% SACC they increased their food intake such that total 23 hr food intake was unaffected. Food intake was not related to the amounts of the different fluids consumed but appeared to be determined by other oral and post ingestion factors associated with the different solutions.     

Diet selection following area postrema/nucleus of the solitary tract lesions

Ten adult Long-Evans male rats were offered access to fat, protein and carbohydrate from separate sources. After adaptation to this diet, 5 animals received thermal lesions of the area postrema and adjacent caudal-medial portion of the nucleus of the solitary tract (AP/cmNTS). The remainder were sham-operated. AP/cmNTS lesioned rats ate significantly less and lost more weight than controls during the first postsurgery measurement period (Days 4–13 after lesioning). The decrease of food intake of AP/cmNTS lesioned rats was due to reduced fat consumption. Carbohydrate and protein intakes of lesioned animals did not differ from those of controls. Food intakes and weight changes of lesioned rats did not differ from those of controls during days 14–23 after lesioning. Intake of fat by lesioned animals remained low but was no longer significantly different from that of controls. Carbohydrate and protein intakes of lesioned rats increased slightly but did not differ significantly from those of nonlesioned controls.     

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.