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After receiving 2.0 mg/kg amphetamine, rats show two phases of reduced food intake, short-term hypophagia, during the first several hours after treatment, and longer-term hypophagia, approximately 19 to 26 hours after treatment. The longer-term hypophagia may be an indicator of an acute withdrawal. This study assessed whether D1 and D2 receptor activation were important early events in the elicitation of longer-term hypophagia. Throughout a series of five-day tests, rats could lever press for food pellets for one-hour periods beginning every three hours. On test day 1, rats were given a saline pretreatment, and fifteen minutes later they were given a saline treatment. On test day 3, they were given a pretreatment of either saline or a selective dopamine receptor antagonist, and fifteen minutes later they were given a treatment of either saline or amphetamine (2.0 mg/kg). In Experiment 1, pretreatments included 3, 12, 31, and 50 μg/kg of the selective D1 receptor antagonist SCH 23390. In Experiment 2, pretreatments included 25, 50, and 100 μg/kg of the selective D2 receptor antagonist eticlopride. Distance moved was monitored for the first six hours following pretreatment-treatment combinations to obtain an indirect behavioral measure of receptor blockade (antagonist attenuation of amphetamine hyperactivity). Food intake at each meal opportunity was monitored throughout each five day test. Patterns of food intake following day 1 saline-saline and day 3 pretreatment-treatment were compared. The combination saline-amphetamine produced short-term and longer-term hypophagia. Combinations involving antagonist-saline did not produce longer-term changes in food intake. Pretreatment with 12 to 50 μg/kg of SCH 23390 produced substantial blockade of amphetamine hyperactivity and prevented amphetamine-induced acute-withdrawal-related longer-term hypophagia. Eticlopride produced a partial blockade of longer-term hypophagia. Both D1 and D2 receptor activation are required for full expression of longer-term hypophagia following amphetamine administration.

Sprague-Dawley rats over-consume calories over a 10 week period and develop diet-induced obesity (c. 100 g body weight differential vs controls) when fed a control pellet diet supplemented with chocolate Ensure liquid. Subsequent withdrawal of Ensure immediately reduces caloric intake by more than 50%, and results in weight loss, despite control pellet being available ad libitum. To assess the molecular underpinnings of this phenomenon, brains were processed for energy balance and food reward-related gene expression analysis at two time points, 24 h and 4 days after the withdrawal of Ensure, when energy intake was suppressed. Gene expression levels in hypothalamic arcuate nucleus and forebrain nucleus accumbens were compared with rats pair-fed to the same energy intake, i.e. imposed negative energy balance, and to controls fed control pellet ad libitum throughout. Cumulative energy intake was approximately 50% lower across the 4 day post-Ensure period, giving rise to a small reduction in body weight although body adiposity and blood leptin remained elevated (c. 100% and 50%, respectively vs controls) in rats that had previously been fed Ensure. In contrast, pair-feeding reduced blood insulin and leptin by 33% and 55%, respectively. Hypothalamic expression of neuropeptide Y and agouti-related peptide was down-regulated at 24 h in rats previously fed Ensure, indicative of the apparent counter-regulatory changes seen in diet-induced obesity, but was normalised between the 24 h and 4 day time points. By contrast, the effect of cumulative negative energy balance in the pair-fed groups increased with time, up-regulating expression of the orexigenic neuropeptides. There was also a reduction of suppressor of cytokine signalling-3 gene expression in pair-fed groups where leptin levels were low. There were no changes in opioid, dopamine receptor or cannabinoid receptor expression in the nucleus accumbens. Feedback from diet-induced obesity appears to drive voluntary hypophagia upon withdrawal of palatable diet, and to override signals from intake restriction that would otherwise set in train an anabolic drive.

Effects of intracerebroventricular (ICV) injection of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on food and water intake were measured in two lines of White Plymouth Rock chickens from a common base population that have undergone long-term divergent selection for either low (LWS) or high (HWS) juvenile body weight. These lines contain anorexic and obese individuals and serve as models for hypo- and hyperphagia. For both ICV injection of CT and CGRP, line HWS responded to a lower dose with decreased food intake than did line LWS. Both peptides were also associated with reduced water intake in both lines. Although plasma glucose concentrations were inherently different between lines, neither CT nor CGRP affected these levels. Comprehensive behavior analyses were conducted and only the number of food pecks was differentially suppressed between lines after both CT and CGRP injection. Thus, the selection program may have caused alterations in the endogenous CT and CGRP systems that synergistically, with other neurotransmitter systems, contribute to the role of food intake on the differential body weights between these lines.

This review article discusses the well-established role of the dorsomedial hypothalamic nucleus (DMN) in feeding, drinking and body weight (BW) regulation. DMN lesions (L) in both weanling and mature rats of both sexes produce hypophagia, hypodipsia and reduced ponderal and linear growth in the presence of normal body composition. The growth reduction is not due to a deficient secretion of growth hormone, insulin-like growth factor-1, thyroxine, triiodothyronine or insulin. DMNL rats actively defend their lower BW (BW settling point) by becoming either hyper- or hypophagic, depending on the experimental manipulation, thereby defending both lean and fat mass. They also regulate their 24-h caloric intake, but they may overeat during the first hour of refeeding following a fast, possibly due to a reduced ability to monitor blood glucose or to respond to cholecystokinin (CCK). 2-Deoxy-D-glucose (2DG) increases c-fos expression in orexin-A neurons in the DMN, and DMNL eliminated the orexigenic effect of 2DG. DMNL rats on high-fat diets do not get as obese as controls, which may be due to a reduction of DMN neuropeptide Y (NPY). Rats lacking DMN CCK-A receptors are obese and have increased expression of NPY in the DMN, supporting earlier data that CCK may act at the DMN to suppress food intake. Excitotoxin studies showed that loss of DMN cell somata, and not fibers of passage, is important in the development of the DMNL syndrome. The DMN is a site where opioids increase food intake and knife-cut studies have shown that fibers traveling to/from the DMN are important in this response. An interaction of glucose and opioids in DMN may also be involved in the control of food intake. DMN knife cuts interrupting fibers in the posterior and ventral directions additively produce the hypophagia and reduced linear and ponderal growth observed after DMNL. Ventral cuts may interrupt important connections with the arcuate nucleus. Lateral and posterior DMN cuts additively produce the hypodipsic effect seen after DMNL, but DMNL rats respond normally to all water-regulatory challenges, i.e., the hypophagia is not due to a primary hypodipsia. The DMN has been shown to be involved in the rat's feeding response to an imbalanced amino acid diet. These data show the DMN has an important role in many processes that control both food intake and BW regulation.

Self-reported effects of stress on eating behaviour and food were assessed in a brief questionnaire in 212 students. Snacking behaviour was reportedly increased by stress in the majority of respondents (73%) regardless of gender or dieting status. The overall increase in snacking during stress was reflected by reports of increased intake of "snack-type" foods in all respondents, regardless of dieting status. In contrast, intake of "meal-type" foods (fruit and vegetables, meat and fish) was reported to decrease during stressful periods. The majority of the respondents reported an effect of stress on overall amount eaten, but while snacking, roughly equal numbers reporting decreased intake (42%) and increased intake (38%). The direction of change in intake could be predicted in part by dieting status, with dieters being more likely to report stress hyperphagia and nondieters being more likely to report stress hypophagia. (C) 1999 Elsevier Science Inc.

To examine the role of the liver in lipopolysaccharide (LPS)-induced hypophagia, we investigated the effect of hepatic portal and vena cava infusions (1 mL/30 min) of LPS (100 microg/kg of body weight) on feeding in rats. LPS infusion significantly reduced food intake when administered via either the hepatic portal vein or the vena cava. Both the magnitude and time course of this hypophagia were similar regardless of the infusion route. As in previous experiments of ours in which LPS was administered by intraperitoneal (i.p.) injection, LPS reduced food intake by decreasing meal frequency, without affecting meal size or duration. The results suggest that peripherally administered LPS does not act primarily in the liver to reduce food intake.

The present study investigated the effect of 48 h of water deprivation on eating behavior of 12 lactating cows fed grass and corn pellets ad lib. Water deprivation reduced grass and corn pellet intake significantly, with corn pellet intake decreasing earlier than grass intake. The reduction of feed intake was entirely due to a reduction of meal size for both grass and corn-pellet meals. The size of the first meal of the water deprivation period was already reduced by about 30%. Grass-meal frequency increased, whereas corn-pellet meal frequency decreased during water deprivation. Water deprivation also decreased live weight and milk yield by about 12 and 30%, respectively. All parameters returned to baseline values with rehydration. With ad lib access to feed and water, 77% of drafts occurred in relation to meals, but the number of meals clearly exceeded the number of drafts. The results demonstrate that water deprivation rapidly leads to premature meal termination. This is in line with the assumption that an enhanced prandial increase in ruminal fluid osmotality contributes to dehydration-induced hypophagia. Yet, further studies are necessary to prove this assumption and to better understand the complex relationships between eating and drinking in ruminants.

It is well known that relatively high doses of epinephrine (E) injected intraperitoneally (IP) produce hypophagia, possibly by an action on liver metabolism. The purpose of the present experiment was to find out if lipoprivation with 2-mercaptoacetate (MA, 800 mumol/kg, IP) or glucoprivation with either 2-deoxy-D-glucose (2DG, 500 mg/kg, IP) or 2,5-anhydro-D-mannitol (2,5-AM, 400 mg/kg, IP) were able to modify the anorectic effect of E (300 micrograms/kg). At the onset of the dark period, mice received a first injection of saline (S) or one of the metabolic blockers mentioned above and, 30 min later, a second injection of S or E; then 30-min food intake was measured. E alone decreased feeding by 80% (p0.05); this effect was nearly the same when MA was previously injected. In contrast, in the presence of 2DG or 2,5-AM, E reduced food intake only by 22% and 24%, respectively (not significant). Attenuation of E-induced hypophagia by these blockers suggests the participation of glucose utilization pathways. Because it has been shown that 2,5-AM acts specifically on the liver, we could additionally suggest that E reduces feeding by an action on glucose hepatic metabolism.

Glucoprivic feeding induced by intraperitoneal (IP) injection of 2-deoxy- d -glucose (2-DG, 250 mg/kg body weight) in the middle of the light phase was investigated in old (age: 15–16 months) and young (age: 2.5–3.5 months) hepatic branch-vagotomized (HBV) and sham-vagotomized (SV) rats. Rats were fed either a carbohydrate-rich diet or a fat-enriched diet a moderate carbohydrate content. The glucoprivic feeding response was greater in 13-h food-deprived old HBV rats than in 13-h food-deprived old SV rats on both diets. 2-Deoxy- d -glucose produced a greater feeding response when rats were fed the fat-enriched diet. Independent of the diet, the transient hyperphagia induced by 2-DG was followed by a long-term hypophagia in old SV rats, but not in old HBV rats. In 13-h food-deprived young rats, hepatic branch vagotomy did not affect the changes in food intake induced by 2-DG. In undeprived old and young rats, the feeding response to 2-DG, exceeding that of deprived rats, was also not affected by HBV. It is concluded that under certain conditions hepatic branch vagotomy eliminates a 2-DG-induced signal inhibiting food intake and thus enhances glucoprivic feeding. The feeding response to 2-DG therefore seems to depend on stimuli affecting food intake in an antagonistic manner.

Mature male rats received bilateral electrolytic lateral hypothalamic area lesions (LHAL) or were sham-operated fed ad lib (CON-ADLIB) or sham-operated pair-fed/gained (CON-PF) to LHAL rats. One month later all rats were sacrificed. Rats with LHAL were hypophagic and had reduced body carcass fat, testes, livers, epididymal fat pads (PADS), diaphragms (DIA), and body weight compared to CON-ADLIB. In the liver, LHAL rats incorporated more C14-U-glucose carbon (GLUCINC) into lipid and glycogen than both CON groups, but GLUCINC was similar among CON groups. In PADS, LHAL rats oxidized more glucose carbon (GLUCOX) than CON-ADLIB but less than CON-PF/PG. The latter showed greater GLUCOX than CON-ADLIB. In DIA, LHAL and CON-PF/PG showed reduced GLUCINC into glycogen vs. CON-ADLIB. Plasma glucose was similar among groups, but insulin was lower in LHAL and CON-ADLIB than in CON-PF/PG. Rats with LHAL had lower plasma T3 concentrations than CON-ADLIB, but similar T3 levels compared to CON-PF/PG. Several of the metabolic changes in LHAL rats could be due to hypophagia; however, four out of nine metabolic indices, glucose carbon incorporation into liver lipid and glycogen and epididymal fat pad lipid and oxidation, were significantly different from CON-PF/PG, i.e., they were independent of food intake. Possibly then, they are due to a lesion effect other than on feeding mechanisms. Some aspects of metabolism that were previously found to be altered 48 h after LHAL were recovered, whereas others apparently were not.

The effectiveness of several different kinds of diets in stimulating hyperphagia in Fischer strain rats was compared. Of three different high-fat diets examined, only one stimulated significant hyperphagia and stimulated weight gain; this diet was high in both fat and carbohydrate. However, this hyperphagia and increased weight gain was transient, lasting less than four weeks. A high-sucrose diet stimulated energy intake for only one week. In contrast, adding water to a high-starch diet or adding saccharin to a wet diet stimulated energy intake and weight gain for at least ten weeks. Once water or saccharin were removed from these diets, hyperphagia subsided or even turned into hypophagia, until body weights approached control levels. The degree of hyperphagia during the first week did not correlate with subsequent hyperphagia or weight gain. These results suggest that wet diets act by different mechanisms than do dry high-fat and high-sucrose diets.

The effects of opioid agonists, morphine (MOR) and ketocyclazocine (KCZ), and antagonists, naltrexone (NALTX) and Mr2266, were investigated on food intake under various conditions, i.e., during light and dark phases of diurnal cycle and free-fed and fasting states in rats. NALTX showed a greater anorexic effect during dark phase, whereas Mr2266 produced such effect during light phase. This suggests that mu-receptors play a major role during dark phase while kappa-receptors are more important in light phase. The comparison of effects of different opioidergic drugs in fasted and free-fed rats showed that NALTX and Mr2266 reduced the elevated basal food intake in 18-h fasted rats to free-fed control levels. Therefore, it appears that enhanced endogenous mu- and kappa-directed neural mechanisms are one of the factors responsible for enhancing food intake in fasted rats. Differential role of MOR and KCZ on food intake in free-fed and fasted rats is also indicated in our study. Both agonists produced a biphasic response in fasted rats, i.e., hyperphagia (0-1 h) followed by hypophagia (1-6 h). However, a generalized hyperphagic effect is observed in free-fed rats (except during 3-6 h by MOR). The initial hyperphagic effect is more prominent in fasted rats which may be due to additive effects of endopioid mechanisms. Specificity of the response at various intervals is confirmed by blockade with NALTX and Mr2266. NALTX appears more potent than Mr2266 in antagonising the effects of MOR but markedly less potent than Mr2266 in inhibiting the effects of KCZ. This suggests that both MOR and KCZ have a mu as well as kappa component in food intake response.

It has been shown that relatively high doses of epinephrine (E) injected intraperitoneally (IP) produce hypophagia and conditioned taste aversion (CTA) in rats. We examined the possibility that E effects involve malaise. For this purpose, changes in saccharin preference induced by E injected IP (100 microg/kg) were determined after a previous administration of trimethobenzamide (TMB, 5 mg/kg), an antiemetic agent. E alone decreased saccharin preference by 54% (p0.01), but only by 16% (not significant) in the presence of TMB. In contrast, the injection of 75 or 100 microg/kg E reduced food intake by 50 and 85%, respectively (p0.01), regardless of previous injection of TMB. In conclusion, the results suggest that E-induced malaise is not the direct cause of the hypophagia it elicits.

Cumulative food intake and plasma glycerol levels following subcutaneous glycerol injections were investigated in rats, because increases in plasma glycerol have been suspected to contribute to glycerol-induced hypophagia. Besides plasma glycerol, plasma non-esterified fatty acids (NEFA), plasma D-(−)-3-hydroxybutyrate (3-HB), blood glucose, and liver glycogen content were also measured. Two daily injections of 80 mg/kg body wt. glycerol did not affect food intake and failed to increase plasma glycerol 30 min after the injection. A single injection of 660 mg/kg body wt. glycerol reduced food intake and increased plasma glycerol 1–2 hours after the injection. This glycerol dose also increased liver glycogen content 1–2 hours after the injection but did not affect plasma NEFA and 3-HB. Rats injected with 660 mg/kg body wt. glycerol did not reduce feeding within the first 2 hours following the injection, when plasma glycerol levels were increased. Inhibition of feeding began at about 3 hours and continued up to 6 hours although plasma glycerol levels had declined to control values 5–6 hours after the injection. It is concluded that metabolic consequences of elevated plasma glycerol levels rather than increases in plasma glycerol levels per se elicit the food intake reduction following exogenous glycerol loads in rats.

Two experiments examined the feeding behaviour and body weight changes of rats returned to a standard chow diet after prolonged periods of cafeteria feeding. In the first, both overweight (ad lib fed) and 'normal' weight (fed a restricted ration of cafeteria foods) cafeteria rats became hypophagic compared to chow-fed rats following their return to chow feeding. However, the overweight rats' hypophagia was initially more severe and was longer lasting. In the second experiment, analysis of meal patterns recorded throughout the first 4 weeks on chow after 26-32 weeks of ad lib cafeteria feeding showed that the hypophagia was due to a reduction in mean meal size (MMS) and meal frequency (MF). Food intake and MMS subsequently recovered to within control levels (by 2-3 weeks), but MF remained persistently low. There was a decrease and then a recovery in eating rate (ER) which paralleled the changes in MMS. The previously cafeteria-fed rats lost only 60% of their excess body weight. These findings are interpreted in terms of a negative contrast effect (changes in MMS and ER) and an inhibitory action of increased adiposity on feeding (affecting mainly MF).

Glucose, glycerol and DL — sodium lactate were injected in various doses by intraperitoneal (IP) and subcutaneous (SC) routes in rats accustomed previously to a 24 hr-feeding, 24 hr-fasting schedule. Administration of isosmolar sodium chloride and measurement of water ingestion served as controls for osmotic effects. The three substances determined a dose-dependent feeding depression in the first half hour when administered IP. SC injections produced a much weaker and non dose-dependent feeding depression. Some doses prolonged the hypophagia up to three or even 24 hr. No relation can be established between the hypophagia and the concurrent hyperdipsia since the last effect does not depend on the route of administration. It is suggested that the hypophagia which followed IP administration was due to information of hepatic origin.

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.)

Three experiments have examined the interaction of adrenalectomy and fenfluramine on food intake, body weight and the binding of guanosine-5′ diphosphate (GDP) to interscapular brown adipose tissue (IBAT). In the first experiment, GDP-binding by IBAT mitochondria from adrenalectomized or sham-operated animals was measured for 3 hr after one of 3 doses of fenfluramine. Fenfluramine stimulated GDP-binding at lower doses in the adrenalectomized animals than in the controls. In the first chronic experiment, adrenalectomy prevented the restoration of normal food intake observed 8–10 days after the beginning of fenfluramine treatment. Adrenalectomy also increased weight loss and enhanced GDP binding to mitochondria from IBAT in rats treated with fenfluramine. In the second chronic experiment, the combination of fenfluramine and adrenalectomy led to a progressive weight loss, continuing hypophagia and stimulation of GDP-binding by IBAT, whereas rats treated with fenfluramine alone showed a recovery of food intake at a stabilized but lower body weight. These data are consistent with the hypothesis that adrenalectomy and fenfluramine disable two separate components of the food intake system and that when combined, produce a profound and persisting disturbance in energy or nutrient balance.

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.

1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.

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.

Much recent evidence suggests a dual and opposite action of insulin on food intake and body weight, Peripherally administered, long acting insulin stimulates weight gain and food intake. On the contrary intracerebroventricularly infused insulin decreases food intake and body weight. It has been suggested that the shift from the nocturnal hyperinsulinism and hyperphagia to the day-time hypoinsulinism and hypophagia depended on the action of insulin on the brain during the night. It has also been hypothesized that the absence of nocturnal hyperinsulinism due to fasting was partly responsible for the hyperphagia observed during the subsequent day-time. In the present experiment, insulin was infused intravenously at various low doses (0.01, 0.025, 0.05 U/hr) during a nocturnal fast. Its effects on the following diurnal free food intake were investigated. It was shown that the experimentally elevated plasma insulin induced a dose-dependent reduction in the day-time feeding response. It was concluded that this reduction is due to the chronic action on the brain of the high plasma insulin level induced by the infusion during the nocturnal fast.

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.

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.

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.

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.

Influence of fecal anorexigenic substance (FS-T) on feeding by Zucker obese rats was compared to that by their lean littermates and Wistar King A rats. FS-T, which has been found to suppress food intake mainly by activation of glucoreceptor neurons in the ventromedial hypothalamus, was injected intraperitoneally in a dose of 7 U/kg at 1930 hr, immediately before the dark period. Potency of FS-T in feeding suppression was much less in the obese rats than in their lean littermates or the Wistar King A rats. Meal size of the obese rats was decreased after the injection, but meal duration was unaffected. The suppressive effect on the lean rats and the Wistar King A rats included decrease of both size and duration of the meal. These results suggest that chemosensitivity in the ventromedial hypothalamus of Zucker obese rats may be impaired, which may be one explanation of the obesity in Zucker obese rats.

The effects of acute exercise (swimming) on food intake (FI) and plasma free fatty acids (PFFA) were examined in male adult rats. FI decreased during the first hour after swimming; it was unchanged during the second hour; it decreased again during the third hour. Body weight decreased over the 24 hours following exercise (-1.7 +/- 1 g) while the animals gained weight during no exercise periods (+3.2 +/- 1 g). At the end of exercise, plasma glucose augmented as well as PFFA levels. An increase in sympathoadrenal activity per se and its inhibitory effect on insulin release can both be responsible for fatty acid mobilization from adipose tissue. Lipolysis could be a cause of hypophagia.