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Eating, drinking, irritability, muricide, and copulation were measured in 45 male rats before and after one of three coronal knife cuts in the septal region or a control operation; in addition, activity was measured postoperatively. (a) Cuts posteroventral to the septum resulted in slight hypophagia, marked hyperdipsia, irritability, asexuality, and decrease in activity. (b) Cuts of the fornix resulted only in slight decrease in activity. (c) Cuts through the anterior septum resulted in irritability, slight hyposexuality, and slight decrease in activity. No significant correlations between the various behavioral effects were found. It was suggested that the neural pathways mediating eating, drinking, irritability, muricide, copulation, and activity are relatively distinct and that neural activity in the septal region probably does not influence behavior in any unitary fashion.

Sustained overeating was induced in rats with repeated daily injections of protamine zinc insulin. The hyperphagia and hypophagia upon termination of insulin treatment were directly related to the amount of insulin that had been administered. The intake was regulatory since animals adjusted food consumption appropriately to compensate for caloric intake from glucose solutions, and they maintained stable caloric intake by reducing the weight of food ingested from a high fat diet. Overeating was unmodified by the use of an equicaloric high protein diet even though total weight gain was reduced. Injections of cycloheximide and dexamethasone prevented protamine zinc insulin induced overeating.

d1-Isoproterenol, a β agonist, injected into the cerebroventricles of satiated sheep and cattle resulted in increased feed intake; however, higher doses caused hypophagia in sheep. The d-stereoisomer was not effective. The responses to isoproterenol could be blocked by β antagonists. 1-Norepinephrine, an α agonist, induced feeding in sheep, but anorexia in cattle. These responses were blocked by α antagonists. 1-Norepinephrine and d1-isoproterenol injected into the hypothalamus during separate tests but in the same loci induced feeding in sheep; however, much less isoproterenol than 1-norepinephrine was required to induce feeding.

Exogenous elevation of circulating ACTH level facilitated the acquisition of a two-way avoidance response at a high but not at a moderate US intensity. Injections of ACTH had no general effect on spontaneous shuttling activity, escape behavior to light-onset, or intertrial responding during avoidance conditioning. Adrenalectomy, which resulted in minimal plasma levels of adrenocortical hormones and, presumably, elevated levels of ACTH, also facilitated avoidance responding. Injection of dexamethasone, a synthetic glucocorticoid and ACTH inhibitor, produced severe weight loss and hypophagia, but did not influence avoidance performance. However, the failure of dexamethasone to affect acquisition of avoidance responding was not related to its effect on body weight and food intake. The action of ACTH on avoidance conditioning is clearly extra-adrenal, but ACTH is not essential to normal performance, at least when high levels of glucocorticoids are present.

Precise electrolytic lesions were placed in the dorsomedial (DMNL) and ventromedial (VMNL) hypothalamic nuclei of weanling rats to study the effect on food and water intake, body weight and length and body composition. Lesions in the DMN consistently resulted in hypophagia, hypodipsia and decreased ponderal and linear growth, both when compared with VMNL rats and with sham-operated controls. The DMNL rats contained more carcass water and lean body mass but less fat than the VMNL rats. The lesion effect persisted in the DMNL rats even after placement of minute lesions of 2.5 mC, while such lesions failed to elicit the changes found with larger lesions in the VMNL rats. The data show that the DMN, at least in the weanling rat, appear to be part of the “feeding center” and water intake circuitry. They also show the minuteness of the area involved and its sharp functional and anatomical delineation from the VMN.

Bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL) of the weanling male rat resulted in hypophagia and hypodipsia, reduced ponderal and linear growth, reduced spontaneous activity, normal carcass fat and increased carcass protein. Previous data in DMNL rats show normal plasma growth hormone, insulin, glucose, cholesterol and triglyceride levels. In the present study, thyroid and testes weights were normal and the reduced metabolic rate is likely due to the profound hypophagia. This makes it unlikely that the poor growth in these animals is due to neuroendocrine disturbances. Rather, it appears to be the result of hypocaloric food intake. Whether the latter is due to a motor failure or a motivational deficit is not established by the present data. The DMN area responsible for the above syndrome is either a primary activity center or a thoroughfare for pathways from other such centers located else-where in the hypothalamus.

Bilateral small stereotaxic lesions limited to dorsomedial part of the amygdaloid complex were made in 10 dogs. It resulted in aphagia with subsequent longlasting hypophagia, adipsia, vomiting and impairment of the acquisition of instrumental alimentary reactions. Also, other changes in behavior were observed such as apathy, lack of motivation, loss of interest in the surroundings and friendly relations with humans, negativism and catatonic-like bizarre postures.

The effect of rapid hypobaric transition (1 hr.) upon water consumption, food consumption, body weight, feeding activity and spontaneous activity of albino rats was studied using a within-subject design. Transition from 635 ± 5 mm. Hg. (5,000 ft.) to 455 ± 5 mm. Hg. (14,000 ft.) induced temporary hypophagia, hypodipsia and concomitant weight loss; gradual recovery occurred during the exposure period; return to 635 ± 5 mm. Hg. after 7 days abruptly (≤ 24 hr.) alleviated these effects. Alterations in feeding activity (time-in-foodwell) during the off portions of the light cycle paralleled food intake changes. No reliable changes in spontaneous activity as a function of hypobaric transition were noted. Results were interpreted as suggestive of hypothalamic and frontal cortex involvement in hypoxia-induced behavioral shifts.

Rats with familial diabetes insipidus (D.I.) were exposed to liquids in which the solute was either excreted (NaCl), metabolized (glucose), or partially excreted-metabolized (milk). In the presence of an isosmotic solution where all the solvent was utilized for clearance of the solute (NaCl), rats continued to drink but displayed aphagia; decrease in the osmolality of NaCl solutions resulted in a proportional recovery of solid food ingestion. Exposure to milk resulted in hypophagia. Glucose solution did not interfere with the maintenance of eating, however, rats with D.I. did not increase their intake of glucose solution during solid food deprivation. Experimental evidence supports the view that the state of hydration as indicated by the body-fluid osmolality is essential for the maintenance of solid food ingestion. The evidence for a primary caloric regulation was doubtful.

Electrolytic bilateral lesions of the dorsomedial hypothalamic nucleus of both female and male mature rats resulted in hypophagia, hypodipsia and decreased spontaneous running activity. The latter is not associated with increased fat deposition. Resting oxygen consumption was reduced in both sexes, but significantly only in the males. Thyroid weight was normal in both sexes but ovaries and adrenals were lighter in the females and the pituitary was lighter in the male rats with lesions. The data show that the dorsomedial hypothalamic nucleus is involved in hypothalamic mechanisms controlling food intake, water intake and spontaneous activity not only in the weanling rat as previously demonstrated, but in the mature rat as well.

Male rats received bilateral electrolytic lesions shortly after weaning in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei, respectively. A third group of rats served as sham-operated controls. The animals were subjected to intragastric preloading with 33% d-glucose and egg-white solutions and a 33% corn-oil suspension, and ad libitum feeding was assessed hourly for the first 7 hr after preloading. The pattern of food-intake depression was similar in all groups but the quantitative greatest depression was found in the DMN rats. The response of these three groups of animals to a diet diluted with 20% alpha cell, a nonnutritive bulker, showed an initial failure to meter calories by both VMN and DMN rats which, however, was compensated for during the remainder of the 24-hr test period. In response to a 50% glucose-chow mixture, both VMN and DMN rats, as well as the controls, showed the same pattern and behaved like mature dynamic hyperphagic rats inasmuch as they did not eat more of this mix than of the standard diet. After a 48-hr fast, both VMN and DMN rats showed refeeding hypophagia rather than hyperphagia. The data suggest that Panksepp's contention that the VMN in the mature rat is involved in long-term satiety regulation may be extended to the weanling rat with VMN destruction. Thus, this controlling role appears established early in ontogeny.

Thus far both the weanling rat ventromedial and dorsomedial syndrome have been investigated in only two and three-week studies. The present data are derived from a six-month study. Food intake and body weight and length changes were recorded weekly or bi-weekly and endocrine and metabolic parameters were assessed at sacrifice. Rats that had received ventromedial hypothalamic lesions shortly after weaning showed all the changes noted in previous short-term studies, i.e. normal body weight gains and food intake but increased carcass fat content. In addition, they manifested a slight hyperglycemia, normal free fatty acid levels and slowingdown of lipogenesis. Rats that had received dorsomedial lesions shortly after weaning also showed changes previously reported in short-term experiments. These include reduced ponderal and linear growth and food intake, but normal carcass composition and growth hormone levels. In addition, they showed a slight improvement of hypophagia with time, and at sacrifice hypoglycemia and low free fatty acid levels. Incorporation of glucose into fat pad glycogen and CO2 was decreased. In diaphragm, glucose incorporation was increased in both total lipid and fatty acids. The data demonstrate that both hypothalamic syndromes change with time, but not necessarily in a progressive manner. They also show that destruction of two so closely appositioned hypothalamic structures brings about entirely different and, in some parameters, opposite changes.

Electrolyte excretion and balance were compared in meal-eating, adlibitum-fed rats maintained in Denver (1,600 m) and on Pikes Peak (4,300 m) and in meal-eating rats maintained in Denver but pair-fed to the Pikes Peak animals. Most of the changes in excretion and balance at Pikes Peak were attributable to hypophagia. At both elevations, equivalent decrements in mineral intake led to nearly equivalent decrements in mineral excretion. Comparisons of the Pikes Peak and Denver pair-fed animals, however, revealed certain changes that were unique to high altitude. These included a marked and sustained reduction in ammonia excretion over the 13-day period of exposure. The higher elevation also produced an enhanced sodium excretion on day 1 of exposure and a reduced sodium balance over the first 6 days. Potassium balance showed no changes unique to high altitude during the first 6 days on Pikes Peak but was significantly reduced during week 2 of exposure. The urinary sodium:potassium ratio was elevated during the first 4 days at 4,300 m, but this effect was attributable to altitude on day 1 only. Enhanced calcium and magnesium excretions, relative to those observed in the pair-fed rats, were observed over the middle and latter portions of the exposure period. The balance of these two minerals showed no altitude-dependent effects. Chloride and phosphate excretions showed an altitude-dependent reduction during day 1 and week 1 of exposure, respectively. These changes were associated with more positive balances. It is concluded that the altitude-dependent effects on mineral metabolism are largely, if not entirely, attributable to hypocapnia and associated alkalosis.

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.

Nicotine, in doses of 0.15 and 0.45 mg/kg, induced hypophagia and hypodipsia in 20 hrs-deprived rats and elevated the threshold currents for hypothalamically induced feeding and drinking in satiated rats. These effects were blocked by pretreatment with 0.5 mg/kg mecamylamine, but not by pretreatment with 3.0 or 9.0 mg/kg hexamethonium. These results indicate a centrally-located mechanism for the hypophagic and hypodipsic effect of single injections of nicotine.

Feeding responses of sheep and steers were compared following intraventricular injection of alpha-adrenergic agonists and antagonists in 2-hr. tests. In sheep, injection of the alpha-agonist 1-norepinephrine (1-NE) (140-1,120 nmoles) increased feed intakes 288% and 388% compared with intakes following synthetic cerebrospinal fluid. This response was blocked by the alpha-antagonist phenoxybenzamine, whereas the antagonist alone decreased feed intake. The beta-adrenergic antagonist propranolol did not modify the 1-NE response. A purer but weaker alpha-agonist, 1-phenylephrine, also resulted in increased feed intake that was blocked by phenoxybenzamine. In contrast to the feeding responses of sheep, 1-NE caused hypophagia in steers, reducing intakes as much as 58% in 2-hr. tests over doses ranging 42-27,800 nmoles. Phenoxybenzamine blocked the 1-NE-induced hypophagia in steers; when injected alone, it increased feed intakes 181% of control values. Changes in feeding following 1-NE injections are probably not attributable to changes in temperature, fat mobilization, or stupor. The data support the hypothesis of an alpha-adrenergic-coded system for feeding in sheep and for satiety in steers.

Four to six weeks after recovery of feeding following lateral hypothalamic lesions, bilateral lesions were made in the habenular nuclei of rats. Although a transient hypophagia was observed in some animals, none showed aphagia or adipsia. This study indicates that the habenular nucleus is not a crucial part of the feeding system which mediates the recovery from aphagia shown by rats with lateral hypothalamic lesions.

Exploratory electrode insertions using a stereotaxic instrument, without passing current, have been made bilaterally in and around the area in the hypothalamus of the rat where electrolytic lesions produce complete aphagia and adipsia. These ‘sham operations’ produce pronounced hypophagia and hypodipsia for 1–2 days. Effect on food intake is large and fairly uniform with all insertions peripheral to these nuclei but increases abruptly in the immediate neighborhood of the nuclei. It is suggested that electrode insertion without passing current may be useful as a finer tool than electrolytic lesions for precise localization of the centers involved.

Localization of lesions in the lateral subthalamic area of rats which produce a high success rate of aphagia is described. Complete adipsia accompanied this aphagia in all cases. The aphagia and the adipsia are separate responses to the lesion. The pattern of material exchange cannot be reproduced by deprivation of sham-operated rats of either food or water. Rats fully sham operated in this area show hypophagia and hypodipsia for 1 or 2 days after operation. Daily intubation of water into operated animals appears to facilitate the escape of animals from the inhibition of eating and drinking. Escaped animals showed a pronounced polydipsia after escape, but this was of a variable degree of permanence and did not always appear consistent in other respects with diabetes insipidus.

Rats were treated with daily i.p. injections of reserpine (0.5 mg/kg) or saline for 10 days. Twenty-four hours after the last injection they were given (+)-amphetamine (0.25, 0.50, or 1 mg/kg) or saline and their locomotor activity was measured for 3 hr. In accordance with previous reports, (+)-amphetamine induced a significantly greater stimulation of spontaneous activity after reserpine. The effect was variable however insofar as it was observed only in those animals that suffered marked weight loss during the reserpine treatment. In addition, when the heightened baseline activity of the groups chronically treated with reserpine was considered, the enhanced stimulant effects of (+)-amphetamine were no longer evident. In a second experiment, the food intake of the chronic saline animals was controlled so that both the reserpine and saline groups underwent similar weight losses during the 10-day injection procedure. In that experiment, chronic reserpine treatment failed on every measure to increase the stimulant effects of (+)-amphetamine. In contrast to the first experiment, on one measure (the lowest dosage which significantly increased activity) the saline pre-treated animals were more responsive to (+)-amphetamine than were the rats pretreated with reserpine. It is suggested that chronic reserpine administration continues to exert a mild sedative action which is completely masked and reversed by the marked increase in arousal which results from the reserpine-mediated hypophagia and weight loss. This starvation-induced arousal appears to interact with amphetamine-mediated locomotor stimulation to produce the increased responsiveness to amphetamine after chronic reserpine treatment.

Publisher Summary In this chapter, various findings with respect to barbiturate actions upon drinking are reviewed. It discusses a range of phenomena and classifies those phenomena in terms of variables and models that describe them. The first model is based upon the notion that hypnotic dosage or some function of it suffices to describe the barbiturate facilitation of drinking. A hypnotic dimension of barbiturate action is discussed in the chapter. An implication of simple additivity of effects of various barbiturates follows from the postulated dimension of action that appears to obtain among barbiturate antagonists but not among barbiturate synergists. The finding that various hypnotic barbiturates facilitated drinking to differing degrees necessitated the postulation of at least one dimension of action other than the hypnotic dimension. The chapter discusses the chronic effects and withdrawal after a chronic barbiturate course. When phenobarbital is given with ad lib , food and water intake rise for a very short time and fall rapidly to control levels. Pentobarbital has no effect under these conditions. The withdrawal of phenobarbital results in a marked hypodipsia and hypophagia. A few days after withdrawal, the animals return to a state comparable to controls in terms of food and water intake.

Lesions were placed stereotaxically in the principal sensory trigeminal nucleus (PrV), the quinto-frontal tract (QFT) and the nucleus basalis (NB) of the pigeon and their effects upon food and water intake were studied. Bilateral lesions of these three “quinto-frontal” structures are followed by periods of aphagia and by a hypophagia whose persistence and severity are approximately proportional to the bilateral extent of the lesion. Such lesions also disrupt the neurosensory control of the consummatory response of feeding. No effects upon food or water were seen following control lesions placed in a wide variety of regions at several levels of the brain, including the hypothalamus. Moreover, despite their marked effects upon feeding behavior, lesions of quinto-frontal structures do not impair drinking. The results have helped clarify previous studies of forebrain mechanisms in feeding behavior and they suggest that PrV, QFT and NB are afferent components of a network of structures controlling feeding behavior in the pigeon.

Male rats of the Wistar strain were fed a control diet (20% casein) and the same diet to which 3% DL-methionine was added, at environmental temperatures of 24 and 7 °C. Effects of methionine feeding at 24 °C were hypophagia, reduced body weight gain, increased kidney weight, decreased liver weight, deposition of iron in the spleen, and paleness of the eyes; there was no effect upon liver fat concentration. At 7 °C, food (and hence methionine) intake was markedly increased in rats fed the methionine-supplemented diet; the accentuation of effects of methionine feeding in these animals might be attributable to the increased intake of this amino acid. In addition, a condition resembling severe frostbite of the ears and paws was observed in these animals. From the results of this experiment it is apparent that the catabolic effect of cold exposure does not eliminate the deleterious effect of excess dietary methionine.

Anatomical studies have identified a network of structures at several levels of the avian brain whose location and connections suggest that they are involved in the neural control of feeding in the pigeon. The network originates in a cranial nerve sensory nucleus innervating the oral region and includes striatal and limbic components. Bilateral lesions placed in several of the structures of this network produced disturbances of feeding and drinking, including aphagia, adipsia, and hypophagia. It is suggested that further neurobehavioral analysis of these structures may clarify the role of extrahypothalamic mechanisms in the neural control of feeding.

A series of rats were lesioned unilaterally through hypothalamic electrodes from which drinking and self-stimulation could be elicited. The lesions abolished electrically-induced drinking and severely reduced rates of self-stimulation. In addition, a transient adipsia and hypophagia resulted from lesioning in several of the animals.

Physiologic studies reported here show that obese persons use carbohydrate, fat, and protein normally during rest and exercise and are not unusually efficient in the use of these energy substrates. Obese subjects mobilize fat stores for energy as readily as normals. It is not necessary to overeat to become obese; the decrease of basal calorie requirements with age is such that obesity can develop with advancing age while exercise remains constant, even if food intake is reduced to some extent. Subjects tested were persons of various ages whose intake of food ranged from that of hypophagia to that of hyperphagia and whose body weights varied similarly.