Feeding Behavior In Rats Research Articles

Effect of intracerebroventricular orexin-B on food intake in sheep.

Orexin is a hypothalamic neuropeptide that regulates feeding behavior in rats. Orexin-B has recently been cloned in pigs and was shown to stimulate food intake after intramuscular injection. This study was designed to determine whether intracerebroventricular (ICV) and intravenous injections of orexin could regulate appetite in sheep. Suffolk wethers were moved to indoor facilities, adapted to diets for 6 wk, and trained to stand in stanchions for 3 to 6 h each day for 2 wk before indwelling ICV cannulas were installed. These sheep were provided water and they consumed feed ad libitum. On the day before an experiment, each sheep was cannulated in a jugular vein. On the day of an experiment, sheep were placed in stanchions and allowed to stand for 1 h before use. Sheep were then monitored over a 2-h control period before i.v. injection with saline or porcine orexin-B (3 micrograms/kg BW) or ICV injection with artificial cerebrospinal fluid (CSF), orexin (0.03, 0.3, or 3 micrograms/kg BW) or in a second experiment with either orexin B (0.03, 0.3, 3 micrograms/kg BW), neuropeptide-Y (NPY; 0.3 microgram/kg BW), or orexin plus NPY. Food intake was monitored for consecutive 2-h periods. The i.v. injections of orexin did not affect food intake or metabolite or hormone concentrations. In ICV sheep, orexin increased food intake at 2 (P < 0.04) and at 4 h (P < 0.02). Food intake was greatest with the 0.3 microgram/kg BW dosage of orexin (P < 0.05). In the first 2 h after injection, orexin had an effect similar to that of NPY (0.23 kg for orexin and 0.2 kg for NPY). The combination of NPY and orexin had a greater effect on food intake (to 0.34 kg) than did either orexin (P < 0.05) or NPY (P < 0.008) alone. Differences were not apparent in the subsequent 2-h interval. No differences were noted in free fatty acid, glucose, growth hormone, luteinizing hormone, or insulin concentrations following orexin injection. There was an effect of ICV orexin treatment on plasma cortisol concentrations (P < 0.002). Cortisol was increased by orexin at the 0- to 2-h (P < 0.008) and in the 2- to 4-h (P < 0.009) intervals after orexin injection. These data indicate that central administration of orexin stimulates feed intake in sheep.

Effect of stress on feeding behavior in rats: individual differences

Abstract The experiment was conducted to study individual differences in stress-induced changes of food intake in rats and to examine concomitant changes of non-eating behaviors. Eating and non-eating behaviors were measured during five consecutive test sessions under stressful noise (95 dB white noise, n =18) and control conditions (60 dB white noise, n =18). Two thirds of the stressed rats were classified as normophagic, one third showed hypophagic responses. Hypophagic rats spent less time eating and more time grooming and resting than normophagic and control rats. Hypophagic rats also showed an increased tendency of scanning movements during eating and an increased tendency to leave the food area. Their eating speed was significantly lower than that of the normophagic rats. Hypophagic rats were characterized by a heightened reactivity to stressors which may have counteracted the adaptation to the stressful feeding situation. Results point to a role of biological factors for individual differences in stress-induced changes of eating.

Dose–response effects of orexin-A on food intake and the behavioural satiety sequence in rats

Although intracerebroventricular (i.c.v.) administration of orexin-A has been reported to stimulate food intake and/or feeding behaviour in rats, mice and goldfish, little attention has thus far been paid to its effects on normal patterns of feeding. In the present study, a continuous monitoring technique was used to characterise the effects of this novel neuropeptide on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Particular attention was devoted to the behavioural satiety sequence, in which feeding is followed by grooming and resting. Although results confirmed the hyperphagic effects of orexin-A (3.33–30.0 μg i.c.v.), gross behavioural analysis failed to reveal any reliable effects of peptide treatment on eating, drinking, sniffing, grooming, resting, locomotion or rearing. However, microstructural analysis revealed behavioural effects of orexin-A that are both dose- and time-dependent. At lower doses (3.33–10.0 μg), orexin-A primarily delayed behavioural satiety, i.e. the normal transition from eating to resting. In contrast, the 30 μg dose initially induced a sedative-like effect, significantly suppressing eating and other active behaviours for the first 15–20 min of the test period. This sedative-like effect resulted in a phase-shifting of the entire behavioural sequence with higher than control levels of eating, grooming, locomotion, rearing and sniffing observed over the second half of the test session. Present findings illustrate the advantages of microstructural behavioural analysis and suggest that the hyperphagic response to low doses of orexin-A results largely from a delay in behavioural satiety while that seen in response to high doses may occur in rebound to initial behavioural suppression. Further studies will be required to confirm the identity of the specific orexin receptors (i.e. OX 1 or OX 2) involved in mediating the dose-dependent behavioural effects reported.

Effect of maternal separation on feeding behavior of rats in later life

Effects of maternal separation on feeding behavior, particularly on rebound hyperphagia, in adult rats were examined. Time-restricted scheduled feeding (2 h per day for 6 days), was given at the age of 3, 6, 9 or 12 weeks in rats that were maternal separated from postnatal days (PD) 1–21 and control rats. Following the time-restricted scheduled feeding, rats were fed freely for 24 h (rebound hyperphagia). Body weight, daily normal food consumption and food consumption during time-restricted scheduled feeding and rebound hyperphagia were measured. Body weight of 3-week-old maternally separated rats were less than those of control rats. There was no significant difference in normal daily food consumption. Food consumption during rebound hyperphagia was significantly increased in 6- to 9-week-old female maternally separated rats, but there was no difference observed in males. Postnatal maternal separation enhanced rebound hyperphagia of female rats in later life. These results indicate that postnatal maternal separation made rats more vulnerable to the development of abnormal feeding behavior in response to food restriction in later life.

Effects of the Cannabinoid Receptor Agonist, HU 210, on Body Weight and Feeding Behaviour of Rats

We have examined the effect of HU 210, a synthetic cannabinoid receptor agonist, on rat body weight and eating behaviour. HU 210 (25, 50 or 100μ kg−1) sub-chronically administered for four days, produced a dose- and time-dependent loss of body weight. At the highest dose the body weight was not regained by the seventh day after the drug was stopped, remaining markedly below that of vehicle-treated animals. Atchuand sub-chronic treatment of fasted rats with HU 210 (50 and 100μ kg−1) significantly inhibited standard food intake; this anorexic effect was still present seven days after the last injection of 100μ kg−1 HU 210. Fasted rats, familiarized with chocolate and acutely treated with HU 210 at 50 or 100μ kg−1 reduced their standard food but not chocolate consumption in a two-choice condition. The results showed that HU 210 exerted a potent and long-lasting reduction of body weight, and that it produced a disrupting effect on the consumption of standard food, but not of chocolate.

Intracerebroventricular administration of melanin-concentrating hormone suppresses pulsatile luteinizing hormone release in the female rat.

Melanin-concentrating hormone (MCH) has been reported to be involved in the regulation of feeding behaviour in rats and mice. Because many neuropeptides that influence ingestive behaviour also regulate reproductive function, the present study was designed to determine if central administration of MCH changes pulsatile secretion of luteinizing hormone (LH) in the rats. Wistar-Imamichi strain female rats were ovariectomized and implanted with oestradiol to produce a moderate inhibitory feedback effect on LH release. The effects of i. c.v. injections of MCH on LH release were examined in freely moving animals. Blood samples were collected every 6 min for 3 h through an indwelling cannula. After 1 h of sampling, MCH (0.1, 1 or 10 microg/animal) or vehicle (saline) was injected into the third cerebroventricle. Because MCH is also reported to affect the hypothalamo-pituitary-adrenal (HPA) axis, which in turn, can influence reproductive function, plasma corticosterone concentrations were determined in the same animals at 30-min intervals during the first and last hours and every 12 min during the second hour of the 3-h sampling period. When expressed as per cent changes, mean plasma LH concentrations after MCH administration were significantly lower in the animals injected with all doses of the peptide compared with vehicle-treated animals; LH pulse frequency was significantly lowered by 1 microg of MCH. Per cent changes in mean plasma corticosterone levels were not significantly affected by MCH administration. These results in oestradiol-treated ovariectomized rats indicate that central MCH is capable of inhibiting pulsatile LH secretion. We have previously shown that 48-h fasting suppresses pulsatile LH release in the presence of oestrogen. Take together, these results raise the possibility that MCH could play a role in mediating the suppression of LH secretion during periods of reduced nutrition.

Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake.

Previous studies indicate that administration of the metabolic inhibitor, 2,5-anhydro-D-mannitol (2,5-AM) or methyl palmoxirate (MP), induces feeding behavior in rats by lowering hepatic energy status. Combined treatment with these agents synergistically increases food intake. The present study was designed to investigate whether combined treatment also has a synergistic effect on hepatic energy status. Rats treated with both inhibitors increased feeding behavior compared with the controls, whereas those treated with 2, 5-AM or MP alone did not. Although 2,5-AM alone lowered hepatic ATP content regardless of MP treatment, only the combination resulted in decreases in hepatic ATP/ADP ratio and phosphorylation potential. MP treatment did not affect the uptake of 2,5-AM into liver. These results suggest that a reduction in hepatic energy status is the common triggering signal for eating behavior induced by 2,5-AM and MP and provide additional evidence for an integrated metabolic control of food intake.

Urocortin in the ventromedial hypothalamic nucleus acts as an inhibitor of feeding behavior in rats

Urocortin (UCN), a member of the corticotropin-releasing factor (CRF) family, inhibits food intake when it is injected intracerebroventricularly in rats. To explore the site of action of UCN in feeding behavior, we examined the effects of injection of UCN into various hypothalamic nuclei on food and water intake in 24-h fasted rats. Injection of UCN into the ventromedial hypothalamic nucleus (VMH) significantly inhibited food and water intake over 3 h without sedative effect, but no significant effect was observed following injection either into the lateral hypothalamic area, or the paraventricular nucleus of the hypothalamus. To further explore the physiological significance of endogenous UCN of the VMH in feeding behavior, the effect of immunoneutralization of hypothalamic UCN on food intake was examined. Injection of anti-rat UCN rabbit γ-globulin into the bilateral VMH in freely fed rats significantly potentiated food and water intake compared with rats that received normal rabbit γ-globulin. These results suggest that endogenous UCN in the VMH exert inhibitory control on ingestive behavior.

Involvement of the caudal raphe nuclei in the feeding behavior of rats.

Involvement of the caudal raphe nuclei (raphe pallidus, RPa; raphe magnus, RMg, and raphe obscurus, ROb) in feeding behavior of adult rats was studied by measuring c-Fos protein expression, in animals submitted to the "meal-feeding" model of food restriction in which the rats were fed ad libitum only from 7:00 to 9:00 h, for 15 days. The experimental groups submitted to chronic fasting, named 'search for food' (SF), 'ingestion of food' (IF) and 'satiety of food' (SaF) were scheduled after a previous study in which the body weight and the general and feeding behaviors were evaluated by daily monitoring. Acute, 48-h fasting (AF) was used as control. In the chronic group, the animals presented a 16% reduction in body weight in the first week, followed by a continuous, slow rise in weight over the subsequent days. Entrainment of the sleep-wake cycle to the schedule of food presentation was also observed. The RPa was the most Fos immunopositive nucleus in the chronic fasting group, followed by the RMg. The ANOVA and Tukey test (P<0.05) confirmed these results. The IF group was significantly different from the other three groups, as also was the number of labeled cells in the RPa in SF and IF groups. Nevertheless, no significant difference was observed between RMg and RPa, or RMg and ROb in the SaF and AF. However, it is interesting to observe that the groups in which the animals were more active, searching for or ingesting food, presented a larger number of labeled cells. These results suggest a different involvement of the caudal raphe nuclei in the somatic and autonomic events of feeding behavior, corroborating the functions reported for them earlier.

Effects of Hunger State on Within-Session Response Decreases under CRF Schedule

Feeding behavior of rats within a single session can be well described as a linear equation of the cumulative amount of food intake. This study investigates the effect of hunger state on the parameters of the equation. Rats pressed a lever to obtain food pellets under a continuous reinforcement schedule. Response rates were regressed to the cumulative amount of intake. Two different manipulations of hunger (food deprivation duration and prefeeding) systematically altered a parameter that represented the amount of food required to terminate a meal. The amount of prefeeding was directly reflected in that parameter. Another manipulation that did not affect hunger (varying the duration of a press required to produce food) did not alter that parameter. These results suggest the parameter (the x-axis intercepts of regression lines) could be a good measure of hunger state.

Administration of Erythromycin dose not Stimulate Food Intake in Fasted Chickens.

Several neural peptides are known to stimulate feeding behavior in mammalian species. Among them, administration of motilin has been found to stimulate feeding behavior in rats and mice. However, central administration of mammalian motilin did not stimulate food intake of the neonatal chick in the previous study. Erythromycin acts as a smooth muscle motilin receptor agonist in mammals, but its effect on feeding behavior has not been investigated. The aim of this study was to elucidate whether administration of nonpeptidergic motilin agonist erythromycin stimulates feeding of fasted neonatal chicks. We administered erythromycin through intraperitoneal and oral routes, since it acts on the gut. No significant effects on food intake were obtained after intraperitoneal and oral administration of erythromycin. We also used the growing (4-week-old) chicken for oral administration of erythromycin, but no significant effect on food intake was obtained. These data suggested that erythromycin did not stimulate feeding in fasted chicks.

Fatty acid oxidation affects food intake by altering hepatic energy status.

Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.

Neural substrate for an integrated metabolic control of feeding behavior.

Evidence indicates that feeding behavior in rats is controlled by a mechanism that integrates information about different aspects of fuel metabolism. We investigated the neural substrate for this integrated control by measuring the effect of metabolic inhibitors given alone and in combination on food intake and neuronal activity as reflected by the expression of c-Fos protein. Combined administration of methyl palmoxirate (5 mg/kg po), an inhibitor of fatty acid oxidation, and 2,5-anhydro-D-mannitol (150 mg/kg ip), which decreases liver ATP content, increased feeding in rats more than expected on the basis of eating responses after treatment with either inhibitor given alone. Combined treatment also produced a synergistic increase in Fos-like immunoreactivity in several brain areas, including the nucleus of the solitary tract, area postrema, and parvocellular portion of the hypothalamic paraventricular nucleus. These findings provide strong evidence for the involvement of selected brain regions in the metabolic control of food intake and suggest that metabolic information used to control feeding behavior is integrated in the periphery or at the level of the brain stem.

Effects of &beta;-cyclodextrin on feeding behavior in rats and dogs

Effects of &beta;-cyclodextrin on feeding behavior in rats and dogs

Melanocortin mediated inhibition of feeding behavior in rats

Melanocortinergic neurons are believed to play a role in the control of food intake. Melanocortin receptor agonists and antagonists modulate feeding in several mouse models of chemically and genetically induced hyperphagia. To date, little information is available describing the role of this neurological system in the control of the natural feeding cycle in genetically intact rats. To evaluate the involvement of melanocortins in spontaneous nocturnal feeding, the synthetic melanocortin receptor agonist, MTII and the antagonist, SHU9119 were administered ICV (third ventricle) alone and in combination. Dose-dependent inhibition or stimulation of food intake was observed with MTII or SHU9119, respectively. Co-injections containing equal concentrations of MTII and SHU9119 resulted in food intake that was indistinguishable from controls. Food intake patterns observed in studies in which various dose combinations of MTII and SHU9119 were co-injected are consistent with the concept that both affect feeding by acting on similar melanocortin receptors. The hypothesis that effects of melanocortins on feeding may be mediated via an NPY related pathway was tested by co-injecting MTII and NPY in a 2-h satiated food intake paradigm. MTII inhibited food intake induced by 5.0 μg hNPY in a dose dependent manner with the highest dose tested abolishing the NPY feeding response. The studies suggest that melanocortins act via specific receptors to control food intake in rats, possibly via an NPY related pathway. If similar neurochemical processes operate in humans, selectively modulating specific melanocortin receptor signaling may be an approach to the treatment of human obesity.

Nitric oxide synthase inhibition attenuates saccharin or ethanol reinforced responding in long-evans rats

1. 1. Effect of 7-nitro indazole (7-NI), brain specific inhibitor of nitric oxide synthase (NOS), on saccharin or ethanol reinforcement was investigated in male Long-Evans rats. 2. 2. Twenty-four rats were trained to lever press both for a 1-% (w/v) saccharin solution and 10% (v/v) ethanol solution using a lever-pressing schedule of progressive ratio. 3. 3. Well-trained rats were tested with 7-NI (10, 20 and 40 mg/kg) or a vehicle (methylcellulose, 2%) injected ip. 60 min before each test. In some tests, L-arginine (1000 mg/kg, ip), a NO precursor, was injected 30 min before a 7-NI (40 mg/kg) injection. 4. 4. Treatment with 7-NI reduced the lever pressing for either saccharin or ethanol reinforcement in a dose dependent manner. The inhibitory effects of 7-NI on the lever pressing for saccharin or ethanol were blocked by L-arginine pre-administration. 5. 5. Our results suggest that reduction in ethanol reinforcement by NOS inhibition may be related to central mechanisms modulating feeding behavior in rats.

Coupling effect of locomotor activity on the rat's circadian system.

Exercise is recognized to affect circadian rhythmicity in a variety of ways. It masks the expression of other behavioral and physiological rhythms, entrains the master pacemaker, and influences the free-running period of other rhythms. In this paper we study the influence of exercise on the organization of the timing system by analyzing the effect of voluntary locomotor activity on the circadian feeding behavior of rats subjected to different lighting conditions. The availability of wheel running prevented loss of feeding circadian rhythmicity under constant bright light (LL) but did not elicit any circadian pattern in rats showing a previous arrhythmic pattern. Under dim red light (DR), the rhythm was more pronounced in exercising than in sedentary rats, while wheel-running availability accelerated the emergence of circadian rhythmicity in arrhythmic animals that were moved from LL to DR. These results can be explained by the existence of a positive feedback loop between physical exercise and its pacemaker and also suggest that exercise changes the functioning of the circadian system to facilitate the emergence of circadian rhythms in previously arrhythmic animals.

Within-session response rate in rats decreases as a function of amount eaten

AOYAMA, K. Within-session response rate in rats decreases as a function of amount eaten. PHYSIOL BEHAV 64(5) 765–769, 1998.—In past studies, within-session changes of rat feeding behavior were always treated as functions of time. This study aimed to describe the within-session decreases of operant response as a function of cumulative amount of food intake. Rats ( n = 8) were trained to obtain food pellets by lever-press responses. Session lengths were 45 min. The following results were observed: 1) Response rates during a CRF schedule were well described as a linear function of cumulative amount of food pellets eaten; 2) The linear equation was also accurate in describing the response rates during a semi-VI schedule; and 3) Even if schedules of reinforcement were changed within a single session, response rates in each reinforcement schedule were well described as linear functions of cumulative food intake. Thus, response rates decreased proportionally to the increase in cumulative amount of food intake.

Temporal relationships between eating behavior and liver adenine nucleotides in rats treated with 2,5-AM.

Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) elicits eating behavior in rats by its action in the liver. To evaluate whether the decrease in liver ATP levels produced by injection of 2,5-AM plays a role in the eating response, we examined the relationship between changes in eating behavior and liver adenine nucleotide levels over time in rats given 2,5-AM. Liver ATP concentrations decreased within 15 min after injection of 2,5-AM (300 mg/kg ip), remained low for up to 90 min postinjection, and returned to control (saline injection) levels by 4 h after treatment. Rats fed ad libitum initiated eating between 15 and 45 min after 2,5-AM treatment, after liver ATP levels had declined. Rats given food 1 h after 2,5-AM treatment increased food intake, but if access to food was delayed for 4 h after 2,5-AM injection the eating response was attenuated or absent. Whereas liver AMP and ADP levels were also altered by injection of 2,5-AM, changes in food intake did not consistently track changes in these nucleotides. The results support the hypothesis that the eating response to 2,5-AM is triggered by a decrease in liver ATP level.

Effects of leptin and orexins on the feeding behavior in rats

Orexin-A and orexin-B are hypothalamic peptides. Orexin-A binds equally to both orexin-1 and orexin-2 receptors but orexin-B has a preferential affinity for orexin-2 receptor. In the spinal dorsal horn, orexins have been shown to be concentrated in the superficial laminae. In the present study, the authors examined the effect of spinally applied orexin-A and orexin-B on the primary afferent fiber-evoked nociceptive reflex in the isolated spinal cord of the neonatal rat. In the isolated spinal cord preparation from 0–3day old rats, single-shock stimulation of a dorsal root (L3–L5) at a strength which can activate C-fibers induced a slow depolarizing response lasting about 30s (slow ventral root potential: slow VRP) in the ipsilateral ventral root of the same segment. Bath application of orexin-A and orexin-B inhibited the slow VRP in a concentration-dependent manner. Bath application of SB-334867, a selective orexin-1 receptor antagonist, had no effect on the depressant effect of orexin-A on slow VRP. Bath application of [Ala11,d-Leu15]-orexin B, a selective orexin-2 receptor agonist, depressed the slow VRP. Both orexin-A and orexin-B depressed the level of temporal summation of synaptic activity evoked by 20 repetitive stimulations of the dorsal root. These data suggest that orexin-2 receptor, but not orexin-1 receptor, may play an inhibitory role in nociceptive transmission in the neonatal rat spinal cord.