Computerized Rat Eater Meter Research Articles

Food intake and meal pattern in response to hyperosmotic-induced dehydration in obese and lean Zucker rats

ObjectivesObese Zucker rats display neurochemical modifications in the brain characteristic of dehydration, but are nevertheless hyperphagic. This suggests that the obese animals can be resistant to dehydration-induced anorexia. The aim of this study was to test the hypothesis by comparing the effects of dehydration on food intake and feeding pattern between obese and lean Zucker rats. MethodsIntracellular dehydration in obese (fa/fa) and lean (Fa/Fa) Zucker rats was induced by replacing drinking water with hyperosmotic sodium chloride solutions (1.8% and 2.7%, consecutively, 4 d each). Daily food intake, meal size, and meal number were measured using an automated computerized rat eater meter before, during, and after the dehydration. ResultsAfter 8 d of hyperosmotic challenge, body weight decreased by 15% and 10% in lean and obese rats, respectively. Obese rats displayed higher food intake and meal size than lean rats before, during, and after the dehydration. Drinking 1.8% and 2.7% sodium chloride solutes decreased gradually food intake and meal size in both lean and obese rats; however, obese rats had a higher percentage of food intake than lean rats during the osmotic challenge. Higher ratios of food to water intake characterized obese rats and the percentage of such ratios in obese versus lean rats were increased during the 2.7% sodium chloride load. Meal number was not affected by dehydration in obese rats, but it was decreased in lean rats during the 2.7% sodium chloride load and remained low during refeeding after the dehydration, when the meal size was increased. ConclusionDehydration-induced anorexia is present in both obese and lean Zucker rats; however, obese rats are more resistant to dehydration by preserving their meal size and food intake. These results support a role for feeding-associated dehydration in the pathogenesis of hyperphagia and obesity.

Nicotine alters the usual reciprocity between meal size and meal number in female rat

Tobacco smoking reduces appetite and body weight (BW). Cessation of smoking leads to hyperphagia and weight gain. Daily food intake (FI) is a function of meal number (MN) and meal size (MZ), i.e., FI=MN×MZ. Under normal conditions, the female Fischer rat has a periodic reciprocal fluctuation between MZ and MN corresponding to phase of estrous cycle. Wide fluctuations between MZ and MN compensate each other to keep FI constant. Nicotine (5 mg/kg BW/day) was infused via osmotic minipump for 7 days. Controls received saline. FI, MZ, and MN were measured by an Automated Computerized Rat Eater Meter. Nicotine significantly decreased BW and FI via a decrease in MZ without compensatory increase of MN. Nicotine cessation led to hyperphagia, normalizing BW loss via an increase in MZ, which exceeded a compensatory decrease in MN. Nicotine significantly prolonged the estrous cycle by an extension of proestrous phase. Nicotine significantly lengthened the intermeal interval (IMI), delaying the start of the next meal and simultaneously decreasing subsequent MZ. Stopping nicotine led to normalization of IMI and MZ. Data show that nicotine alters the usual reciprocal regulation between MZ and MN and leads to a prolongation of the estrous cycle.

Gender differences in tumor-induced anorectic feeding pattern in Fischer-344 rats

Gender differences of feeding pattern in normal male and female rats are well recognized. Differences in gender-related feeding patterns have also been established following a variety of experimental manipulations, such as hypothalamic lesions, nicotine infusion, and total parenteral nutrition administration. Anorexia is a common feature during tumor growth. The present study examined whether the feeding indices constituting the feeding patterns differed with the development of cancer anorexia in male and female rats. Sixteen male and 15 female Fischer-344 rats had their food intake (FI) and feeding indices, meal number (MN) and meal size (MZ), continuously measured by a computerized rat eater meter. Viable methylcholanthrene (MCA) sarcoma cells (10 6) were inoculated subcutaneously in 10 male (M-TB) and 8 female (F-TB) Fischer rats, while the rest were controls and received an equal volume of vehicle. Tumor-bearing (TB) rats became anorectic by Day 18, when the weight of the tumor was approximately 8% of the total body weight (BW). A notable decrease in BW was observed in both M-TB and F-TB. A decrease in FI resulted from different feeding indices between male and female rats. In male rats, lower FI was due to a decrease in both MN and MZ. In female rats, lower FI was solely due to a decrease in MN. The data show that gender differences in feeding patterns, which are an external manifestation of biochemical changes in the brain, occur following development of cancer-related anorexia suggesting that besides other factors, cancer anorexia is also influenced by sex-related hormones.

Differential feeding patterns induced by tumor growth and by TPN

The effects of anorexia induced by early tumor, and anorexia induced by total parenteral nutrition (TPN) on food intake and the indexes of food intake, were investigated in rats infused with saline after jugular catheter placement and concomitant inoculation with methylcholanthrene (MCA)-induced tumor cells on day 0, and in rats without catheters receiving tumor only. Tumor became palpable around day 10 and increased to represent 6–8% of host body weight by day 26. On day 18, food intake started to decrease. Catheter-bearing rats were then randomized to saline controls ( n = 9) for 11 d or to TPN-100 ( n = 9) for 4 d providing 100% of daily caloric needs. Both then received saline until day 26. Food intake and feeding indexes were continuously measured using the Automated Computerized Rat Eater Meter (ACREM) and data was analyzed using ANOVA and regression analysis. In controls (both with and without catheter) the tumor induced a specific feeding pattern which consisted of a significant ( P < 0.01) decrease in food intake via a significant ( P < 0.05) decrease in meal size. A non-significant decrease in meal number and meal duration occurred. Two other feeding-related activities, meal consumption rate and intermeal sniffs, also decreased. Infusion of TPN-100 into the already anorectic rat led to a further significant ( P < 0.0001) decrease in food intake via a significant decrease in both meal size ( P < 0.0001) and in meal number ( P < 0.0001). A decrease in all other feeding indexes also occurred, resulting in a different feeding pattern. After stopping TPN-100, the TPN-100–induced feeding pattern returned to that of the tumor-induced feeding pattern. That the tumor-induced feeding pattern differs from the TPN-100–induced feeding pattern suggests that the mechanisms whereby these two factors induce anorexia may also differ.

Potential Strategies for Ameliorating Early Cancer Anorexia

Background.Normally the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) interact to regulate food intake (FI), the product of meal number (MN) and meal size (MZ), by changes in neurotransmitters, mainly dopamine and serotonin. Change in LHA dopamine influences meal size; while in VMN, decreasing dopamine and increasing serotonin levels influence meal number. Whether this situation exists in early cancer anorexia was tested in a series of studies to examine the role of the hypothalamus in the pathogenesis of early cancer anorexia.Materials and Methods.In experiment 1, male Fischer tumor-bearing (TB) rats and weight-matched controls had FI, MN, and MZ measured continuously via a computerized rat eater meter. At onset of anorexia, feeding patterns were measured. In experiment 2, the VMN was temporarily blocked with 0.32 μg of colchicine in TB rats, while TB controls had an equal volume of intra-VMN saline, and changes in feeding patterns were measured. In experiment 3, changes in VMN dopamine and serotonin were measured via microdialysis at anorexia and after tumor resection.Results.In experiment 1, with the onset of anorexia, food intake decreased significantly in TB rats, initially by a decrease in MN and then by a decrease in both MN and MZ. No change occurred in controls, suggesting that VMN versus LHA played a more significant role in mediation of cancer anorexia. In experiment 2, following VMN block, FI increased significantly in anorectic TB rats, achieved by an almost exclusive increase in MN with minimal change in MZ, thus supporting the role of the VMN in anorexia. In experiment 3, at the onset of anorexia, FI decreased significantly in TB rats versus controls. TB rats had a significant increase in VMN serotonin and a significant decrease in VMN dopamine. After tumor resection, food intake improved and high levels of serotonin normalized with no change in dopamine.Conclusion.Serotoninergic and dopaminergic systems are involved in the etiology of cancer anorexia. The changes in food intake are mediated via the VMN by a decrease in meal number.

Mode of food intake reduction in Lewis rats with indomethacin-induced ulcerative ileitis

The mechanism of anorexia in inflammatory bowel disease is poorly understood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Crohn's disease. The anorexia of indomethacin-induced ulcerative ileitis was compared with that of the well-known anorexia of total parenteral nutrition (TPN). Forty-five female Lewis rats were randomized to four groups: Control, Indomethacin, Indomethacin + TPN, and TPN. Feeding indices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), prostaglandin E 2 (PGE 2), and leukotriene B 4 (LTB 4) were assayed in plasma, mononuclear cell culture, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primarily via reduction in meal number (MN, 54%; p < 0.05) and, to a lesser extent, meal size (MZ, 35%; p < 0.05). In comparison, in the Indomethacin group SFI decreased (74%; p < 0.05) primarily via reduction in MZ (67%, p < 0.05); MN also decreased but to a lesser extent (27%; p < 0.05). In the Indomethacin + TPN group, SFI decreased (55%; p > 0.05) primarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slightly (19%; p < 0.05). Only in the Indomethacin group were IL-1α and TNF-α detected in the mononuclear cell culture and plasma, respectively. In the Indomethacin group, an inverse correlation existed between MZ and TNF-α ( p < 0.05). In the Indomethacin group, IL-1α, PGE 2, and LTB 4 concentrations did not correlate with feeding indices. SFI reduction in this model was mediated primarily via a decrease in MZ. TNF-α is proposed to mediate this effect and TPN was shown to overcome the effect on MZ.

The gut-brain brain-gut axis in anorexia: Toward an understanding of food intake regulation

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes—thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

The gut-brain brain-gut axis in anorexia: toward an understanding of food intake regulation.

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes--thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

The early cancer anorexia paradigm: changes in plasma free tryptophan and feeding indexes.

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia.

Dynamics of oral intake resumption after general anesthesia and operation in rats.

The influence of general anesthesia and operation on dynamics of postoperative food intake resumption was investigated in eight rats. A laparotomy was performed on each rat under anesthesia induced by intraperitoneally injected chloral hydrate. Spontaneous food intake and feeding indexes were continuously measured using an Automated Computerized Rat Eater Meter (ACREM) before and after operation. Although spontaneous food intake and all feeding indexes were depressed immediately following anesthesia and operation, each feeding index was depressed to a greater degree during the dark vs. the light cycle. Initially, rats fully capable of eating ate fewer, smaller, and shorter meals. The return to normal of each feeding index differed temporally. Thus, although meal number normalized by the third postoperative day, meal size by the sixth postoperative day, and meal duration by the fourth postoperative day, normalization of meal number during the light cycle occurred sooner than during the dark cycle, while the converse occurred with meal size and meal duration.

Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.

Nocturnal cyclic versus continuous total parenteral nutrition: Food intake and feeding pattern in rats

Total parenteral nutrition (TPN), providing the equivalent of 100% of mean daily oral intake for 24 hours, depressed spontaneous food intake (SFI) in rats by a mean >80%. Whether TPN had the same effect on SFI when given either in 12-hour cycles (Cyclic-TPN) or in 24 hours (Continuous-TPN) for 8 days was tested in 16 rats with jugular catheters, placed in metabolic cages modified with an Automated Computerized Rat Eater Meter. This continuously measures food intake and its dependent indexes: meal number, meal size, meal duration, meal sniffs and intermeal sniffs. Both rat groups ate the same amounts of chow before TPN. On starting TPN, food intake decreased by >80% in Cyclic-TPN and >50% in Continuous-TPN during each first infusion period. A nadir in food intake was reached in 48 hours with Cyclic-TPN and in 72 hours with Continuous-TPN. Thereafter, there was no food intake during the 12 hours of Cyclic-TPN, with minimal food intake during the intervening 12 hours of non-TPN normal saline infusion period. In both forms of TPN infusion, a reduction in food intake was achieved by a reduction in meal number and size, and thus in meal duration. Feeding-related sniffing activity was decreased by similar amounts with Cyclic- or Continuous-TPN. Cyclic-TPN for 12 hours had no advantage over Continuous-TPN, in that there was no compensatory enhancement of food intake and meal-related behavior during the cyclic non-TPN normal saline period.

Effects of continuous graded total parenteral nutrition on feeding indexes and metabolic concomitants in rats

The influence of graded amounts of total parenteral nutrition (TPN) on food intake and feeding indexes was investigated in 90 rats housed in Automated Computerized Rat Eater Meter metabolic cages with free access to water and chow. When food intake was stable after catheter placement, 10 control rats continued with the 3 ml/h normal saline used for catheter patency, whereas study rats were given graded TPN continuously for 3 days, amounting to the equivalent of 26% (TPN-26), 53% (TPN-53), 81% (TPN-81), or 114% (TPN-114) of their daily caloric needs. TPN consisted of glucose, fat, and amino acids in the caloric ratio of 50:30:20. In study rats, the graded TPN depressed food intake, meal number, meal size, and eventually food consumption rate, meal sniffs, and intermeal sniffs in a dose- and time-dependent manner. During graded TPN, rats decreased total food intake by eating fewer, smaller, shorter meals at a decreasing consumption rate; sniffing activities were correspondingly curtailed. Stopping TPN led to normalization of feeding indexes. Blood glucose did not change while plasma insulin rose with graded TPN. A decrease in hepatic glycogen and an increase in hepatic triglycerides occurred. Plasma valine, phenylalanine, and methionine rose in a TPN dose-dependent manner. TPN-26 and TPN-53 significantly decreased whole brain amino acids; with TPN-114 no change occurred. Brain influx of tryptophan remained unchanged, but a progressive decrease in brain influx of tyrosine occurred. Whole brain dopamine and serotonin were depressed with TPN-26 and TPN-81 but were normal with TPN-114.(ABSTRACT TRUNCATED AT 250 WORDS)

Automated computerized rat eater meter: Description and application

A real-time Automated Computerized Rat Eater Meter was developed by modifying commercially available metabolic cages. Food access via a feeding tunnel was monitored by photocells. Food consumption was measured by an electronic scale. The signals thus generated were processed by a computer. This allowed us to continuously measure the spontaneous feeding behavior of free-feeding nondeprived Fischer rats for a sum total of 35 study days. Based on our data, we defined a meal as an episode of food consumption preceded and followed by at least 5 minutes of no feeding. Fischer rats showed periodic nychthemeral eating behavior. Food consumption, number of meals, meal sniffs, intermeal sniffs, and, consequently, eating activity were greater during the dark cycle than the light cycle. Meal duration, meal size, and thus food consumption rates remained constant throughout both cycles. Our modification of commercially available metabolic cages provides unique data for continuously monitoring rat feeding patterns over prolonged periods of time.

Animal Behavior and Internal Drives

Animal Behavior and Internal Drives