The effects of septal area lesions on the meal patterns of female rats

Measures of food intake and body weight were compared in female rats with sham or septal area lesions. In addition, the pattern of food intake during the day and the night was analyzed into meal sizes and post meal intervals. Postoperatively sham and septal rats were comparable in that both maintained stable food intake and body weight over the testing period. However, the analysis of meal patterns showed that septal rats ate very small, frequent meals relative to sham rats. Since this type of feeding pattern is also seen in animals with gastrointestinal motor deficits, it is suggested that the motor aspects of feeding should be investigated in rats with septal lesions.     

Effect of guanethidine sympathectomy on intake and body weight of intact and LHA-lesioned rats

The present study investigated the role of direct sympathetic nervous system innervation of the viscera in the reduced body weight levels maintained by animals bearing lesions of the lateral hypothalamic area (LHA). Adult, male rats with, and without, electrolytic lesions of the (LHA) were treated with guanethidine sulphate (25 mg/kg IP daily for 6 weeks) to produce destruction of the peripheral sympathetic nervous system. LHA-lesioned rats displayed the expected reduced body weight compared to intact rats. Sympathectomy in lesioned rats resulted in an identical pattern of effects to that seen in intact rats. Transitory reductions in intake were effected and weight was significantly depressed by one week of guanethidine treatment. However, weight had recovered to control levels in both intact and lesioned drug-treated groups by the end of the experiment. The reduced body weight level maintained by LHA-lesioned rats was not altered by guanethidine sympathectomy. The major conclusions are (1) the reduced body weights maintained following LHA lesions are not dependent upon an intact sympathetic nervous innervation of visceral organs, and (2) peripheral sympathectomy in intact adult rats has no chronic effects on either body weight or food and water intake.     

Effects of septal and amygdaloid lesions on discrimination, eating and drinking

Rats were given preoperative training on a visual discrimination task for which lever pressing in the presence of a cue light was continuously reinforced with food. Bilateral septal lesions increased nonreinforced responding, while bilateral amygdaloid lesions reduced responding under conditions of both reinforcement and nonreinforcement. Food intake relative to preoperative body weight increased for the septal lesioned animals. Decreased water intake relative to preoperative body weight and weight reduction were displayed by the amygdaloid lesioned rats. Possible interpretations of the results are discussed.     

Area postrema lesions produce feeding deficits in the rat: Effects of preoperative dieting and 2-deoxy-D-glucose

To investigate the possible role of the area postrema (AP) in the control of food intake and body weight, male albino rats were divided into four groups: (a) animals dieted to 80% of their original body weights prior to receiving AP lesions, (b) nondieted animals with AP lesions, (c) animals dieted to 80% prior to receiving sham lesions, and (d) nondieted animals with sham lesions. Lesions of the AP in nondieted rats resulted in hypophagia, hypodipsia and body weight loss followed by recovery of normal intake and maintenance of body weight at a fixed percentage of the sham operated animals' weight. Reducing body weight prior to surgery led to body weight maintenance levels equivalent to those of the nondieted groups. We also tested the animals for sensitivity to glucoprivation caused by intraperitoneal injections of 2-deoxy-D-glucose (2-DG). Injections of 2-DG produced hyperphagia in sham lesioned rats, but not in rats with AP lesions. Our data suggest that the effects of AP lesions on intake and body weight are similar, in several important respects, to the lateral hypothalamic feeding syndrome and to the effects of subdiaphragmatic vagotomy. We discuss the results with respect to hierarchical levels of neural circuitry involved in controlling feeding behavior.     

Effects of selective estrogen receptor agonists on food intake and body weight gain in rats

Ovariectomized (OVX) rats eat more and gain weight more rapidly than sham-operated (SO) rats and estradiol (E(2)) treatment attenuates food intake and body weight gain in OVX rats. Studies were designed to test the hypothesis that the alpha subtype of the estrogen receptor (ERalpha) mediates the attenuating effects of E(2) on food intake and body weight gain while the beta subtype (ERbeta) mediates opposing actions that lead to increased food intake and body weight gain. Female rats were SO or OVX and treated daily with vehicle (dimethylsulfoxide, DMSO) or E(2) (10 microg/day), or the ERalpha-selective agonist, 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 0.5 mg/day), or the ERbeta-selective agonist, 2,3-bis(4-hyroxyphenyl)-propionitrile (DPN, 0.5 mg/day) for 14 days. Total food intake was significantly reduced by E(2) and PPT, but not DPN. Total body weight gain was significantly increased in OVX rats compared to SO rats and treatment with E(2) or PPT, but not DPN, significantly decreased total body weight gain to levels that were not significantly different from SO rats. A dose-response study of PPT indicated that at 0.25 mg/day, PPT significantly reduced total 21-day food intake and body weight gain and, at 0.13 and 0.06 mg/day, PPT significantly reduced total body weight gain compared to OVX rats without significantly reducing total food intake. A dose-response study of DPN indicated that none of the three doses of DPN significantly altered total 21-day food intake or total body weight gain. These results suggest ERalpha mediates the attenuating effects of estrogens on food intake and body weight gain while ERbeta has no effect on these variables.     

Long-term effects of insulin in weanling rats with dorsomedial hypothalamic hypophagia: Food intake,efficiency of food utilization,body weight and composition

Twenty-five day-old Sprague-Dawley rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. Two weeks after the operation the DMNL rats showed reduced (p<0.001) body weight and food intake but normal body composition (Lee Index) and efficiency of food utilization (EFU). During the following 32 days subcutaneous administration twice daily of intermediary-acting insulin in increasing doses (mean daily dose 2.64 IU/kg) caused highly significant increases in food intake in both groups. Injection for the subsequent 14 days of higher doses of insulin (mean daily dose 5.64 IU/kg) caused dramatic increase in both food intake and Lee Index and equalized the rate of weight gain with that of the controls. However, in absolute terms the DMNL rats remained consistently hypophagic and weighed significantly less than the controls. Both DMNL rats and controls showed the same EFU during both periods of insulin administration. On discontinuation of hormone treatment during the subsequent 20 days, food intake and body weight gains returned to pretreatment values and the insulin-induced increased Lee Index returned into the low-normal range. However, EFU was significantly (p<0.05) decreased during this period. At sacrifice, plasma glucose, glycerol, free fatty acids and total protein and carcass lipid and protein were normal in the DMNL rats. Absolute and relative (per 100 g body weight and per metabolic size) weight of epididymal fat pads, pituitaries, adrenals and kidneys were normal in the DMNL rats but testes weight per 100 g body weight was higher (p<0.05) in the DMNL rats. Although DMN lesions may remove some glucose-sensitive elements within the hypothalamus, the animals are still capable of responding to the food intake and weight-promoting properties of insulin, as do intact animals.     

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.     

Response to chronic insulin administration: effect of area postrema ablation

The effects of daily administration of protamine zinc insulin (PZI) on plasma insulin and glucose levels and on food intake and body weight of rats with lesions of the area postrema and adjacent caudal-medial portions of the nucleus of the solitary tract (APX rats) were examined. Prior to insulin treatment, APX rats weighted less and had lower plasma immunoreactive insulin (IRI) levels than nonlesioned controls but did not differ from controls in plasma glucose levels. Five daily injections of 5 U/kg PZI raised plasma IRI and lowered plasma glucose levels similarly for both lesioned and nonlesioned rats. When injected with increasing doses of PZI over a 30-day period, both lesioned and nonlesioned rats showed increases of food intake and rate of weight gain in response to 8 U/kg PZI. These data indicate that APX does not affect either physiological or behavioral responses to chronic peripheral insulin administration.     

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.     

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.     

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.     

Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: Evidence from a restriction-refeeding regimen

Male rats maintained their body weight at approximately 85% that of sham-lesioned controls following lesions of the lateral hypothalamus (LH). One month following surgery, the food intake of half the LH-lesioned animals was restricted until their body weight had declined to 80% that of nonrestricted LH animals. Half the sham-lesioned animals were similarly restricted until their body weight fell to 80% that of nonrestricted control animals. When returned to an ad lib feeding schedule, both restricted groups were initially hyperphagic and quickly restored their body weights to the level of the nonrestricted group from which they were originally selected. In doing so, the LH animals increased their food intake by the same amount and took the same number of days to restore their weight to control levels as the sham-lesioned animals. These observations provide further evidence of the vigor and effectiveness with which LH animals defend their reduced level of maintained body weight.     

Feeding conditions and estrous cycle of female rats under the activity-stress procedure from aspects of anorexia nervosa.

The present study investigated the application of female rats with activity stress as an animal model for anorexia nervosa. Young female rats were singly housed in activity-wheel cages with food-restricted schedule (2, 3, or 4 h of food availability per day) for 3 weeks. Estrous cycle, body weight, food intake, and wheel revolution were recorded daily. Gastric pathology was also observed using the endoscopic technique. Rats that were subjected to either a 3- or 4-h feeding schedule exhibited the cessation of estrous cycle, loss of body weight, and suppression of food intake. These animals also showed a remarkable increase in running activity. However, they had no gastric lesions throughout the experimental period. On the contrary, the 2-h feeding schedule elicited severe gastric lesions and high mortality. The results suggest that behavioral and physiological changes of the young female rats with 3 or 4 h feeding share some symptoms of anorexia nervosa, although their anorexia is not self starvation.     

Sleep deprivation of rats: the hyperphagic response is real

STUDY OBJECTIVES: Chronic sleep deprivation of rats causes hyperphagia without body weight gain. Sleep deprivation hyperphagia is prompted by changes in pathways governing food intake; hyperphagia may be adaptive to sleep deprivation hypermetabolism. A recent paper suggested that sleep deprivation might inhibit ability of rats to increase food intake and that hyperphagia may be an artifact of uncorrected chow spillage. To resolve this, a palatable liquid diet (Ensure) was used where spillage is insignificant. DESIGN: Sleep deprivation of male Sprague Dawley rats was enforced for 10 days by the flowerpot/platform paradigm. Daily food intake and body weight were measured. On day 10, rats were transcardially perfused for analysis of hypothalamic mRNA expression of the orexigen, neuropeptide Y (NPY). SETTING: Morgan State University, sleep deprivation and transcardial perfusion; University of Maryland, NPY in situ hybridization and analysis. MEASUREMENTS AND RESULTS: Using a liquid diet for accurate daily measurements, there was no change in food intake in the first 5 days of sleep deprivation. Importantly, from days 6-10 it increased significantly, peaking at 29% above baseline. Control rats steadily gained weight but sleep-deprived rats did not. Hypothalamic NPY mRNA levels were positively correlated to stimulation of food intake and negatively correlated with changes in body weight. CONCLUSION: Sleep deprivation hyperphagia may not be apparent over the short term (i.e., < or = 5 days), but when extended beyond 6 days, it is readily observed. The timing of changes in body weight and food intake suggests that the negative energy balance induced by sleep deprivation prompts the neural changes that evoke hyperphagia.     

Food and water intakes of rats as a function of strain,age, temperature,and body weight

Are there age-related differences in the responsiveness of feeding, drinking, and body weight of rats to changes in the environmental temperature and are these differences related to strain of rats? An experiment was carried out according to a 2 by 3 by 3 design, representing strain (ACI/Mai vs Fischer 344), age (young, 217–221 days, mature, 387–391 days, and old 749–753 days), and ambient temperature (21°, 28°, and 32°C). The dependent variables were: g food eaten, g water drunk, g body weight during a single 24 hr exposure to one of the temperatures. The results indicated that food intake per rat was positively related to age and independent of strain. Both strains increased water intake with increasing age, but the Fischer rats did so at a higher rate. While the ACI rats increased body weight with increasing age, the Fischer rats increased body weight then decreased it. However, relative to body weight or food intake, Fischer rats overate and overdrunk and the ACI rats did not. After these strain-age differences in initial levels were controlled statistically, and regardless of strain, theold rats ate more than the young and mature rats at 21°C, more than the young rats at 32°C, the same as the young and mature rats at 28°C, and drank more than the young and mature rats at all temperatures. These results suggest that the mechanisms mediating feeding and drinking remain intact and responsive to the energy and water needs of the rat over a large part of its life-span.     

Dorsomedial hypothalamic lesions at weaning and ovariectomy after maturity: Somatic and metabolic changes

Weanling Sprague-Dawley rats received lesions in the dorsomedial hypothalamic nuclei or sham operations. Analysis of variance revealed a significant lesion-induced depression of body weight (BW) and food intake (FI). After sexual maturity, bilateral ovariectomy (OVX) and/or sham-ovariectomy (S-OVX) were performed in each of the above groups. OVX produced a significant increase in BW in both lesioned and non-lesioned rats without changes in food intake. Following DMN lesions efficiency of food utilization (EFU) was greater than normal and OVX caused a further significant increase, irrespective of hypothalamic manipulation. DMN lesions, as previously shown, were followed by a reduction in linear growth; subsequent OVX exerted a growth-promoting effect in both DMN-lesioned and sham-lesioned rats. However, OVX did not alter plasma growth hormone or insulin levels. When calculated on the basis of per gram tissue protein, DMN lesions significantly diminshed the incorporation of glucose into lipids of diaphragm and fat pad, but not of liver. DMN lesions had no effect on the incorporation of glucose into glycogen of diaphragm, fat pad or liver. OVX did not produce significant changes in lipogenesis from glucose or incorporation of glucose into glycogen in either sham-lesioned OVX or DMN-lesioned OVX rats. The data support the concept that increased weight gain following OVX can be attributed to factors other than increased food intake. They also support previous findings that DMN lesions lower the BW “settling point” (i.e., both lean body mass and fat commensurately). The data also suggest that the DMNL rat is responsive to various manipulations—in this case OVX—of the adipose tissue mass “settling point”.     

Reappearance of dynamic hyperphagia during the static phase in medial hypothalamic lesioned rats

Female rats overate and became obese following electrolytic lesions of the medial hypothalamus. While every animal displayed the characteristic dynamic-static hyperphagic syndrome, not all of them maintained a permanent static phase. After many weeks or months of maintaining body weight at an elevated obese plateau with near-normal food consumption, several of the rats which had at least doubled their preoperative body weight displayed a spontaneous renewal of hyperphagia that was longer lasting and nearly equal in amplitude to the initial dynamic phase. Only one of the less obese animals displayed the phenomenon. The sudden increases in food intake and body weight were not due to a change in diet or any of the other variables which are known to influence the eating habits of obese lesioned rats.     

Body weight gain, food intake and adrenal development in chronic noise stressed rats

Wistar chronic treated rats (30 days) were used to investigate the effect of hypothalamic-pituitary-adrenal activity on growth, food intake and adrenal development (weight and DNA content). The animals were submitted to noise stress, ACTH administration and dexamethasone suppression test. Noise stress decreased body weight gain and food intake. No adrenal hypertrophy was observed but an increase in relative DNA content by stress has been found. ACTH and dexamethasone treated rats showed a body weight and food intake decrease vs. controls. The effect on body weight was higher in dexamethasone treated rats. Adrenal hypertrophy and hyperplasia were found in ACTH treated rats, whereas dexamethasone provoked adrenal atrophy with a decrease in DNA content.     

The ingestion of food and the recovery of body weight following fasting in the naive rat

The total food consumption of experimentally naive rats following 24, 48, 72, and 96 hr fasts was observed during the period of the recovery of body weight. The total amount of food consumed in excess of prefast food consumption was found in all groups to be equivalent to 24 hr intake and was, therefore, independent of degree of fast and body weight lost. Moreover, it was found that rats recover lost body weight following a fast even when intake is held to prefast levels. These findings suggest that the regulation of body weight may be under the control of mechanisms in addition to the control of food intake.     

Regulatory and secondary water intake in rats with lesions of the zona incerta.

Bilateral electrolytic lesions of the zona incerta (ZI) permanently reduced daily water intake of rats by 20-30%. Lesioned rats did not differ from controls in daily food intake, body weight, hematocrit, or serum osmolality, Na+ or K+ levels. The hypodipsia was not caused by changes in water requirements or excretory function or by a nonspecific depression of behavior. Compensatory reductions in water losses maintained fluid balance. Lesioned rats drank as much water as controls in response to intracellular and extracellular dehydration, but unlike controls, appeared to restrict their daily water intake to these regulatory responses. Lesions of the ZI attenuated the ingestion of extra water observed when rats were maintained on a liquid diet adequate to meet fluid requirements, and daily water intake of lesioned but not control rats closely followed changes in water needs. It was concluded that lesions of the ZI reduce daily water intake towards minimal requirements for fluid balance by attenuating secondary drinking (drinking independent of water needs for fluid homeostasis.