Ingestive Behavior In Rats Research Articles

Nucleus accumbens GLP-1 receptors influence meal size and palatability.

Recent evidence suggests that the glucagon-like peptide-1 (GLP-1) neuronal projection to the nucleus accumbens core (NAcC) contributes to food intake control. To investigate the role of endogenous stimulation of GLP-1 receptors (GLP-1R) in NAcC, we examined the effects of the GLP-1R antagonist exendin-(9-39) (Ex9) on meal pattern and microstructure of ingestive behavior in rats. Intra-NAcC Ex9 treatment selectively increased meal size relative to vehicle in rats consuming 0.25 M sucrose solution or sweetened condensed milk. Microstructural analysis revealed effects of NAcC Ex9 on initial lick rate and the size and duration of licking bursts in rats consuming 0.1 or 0.25 M sucrose, suggesting that blockade of NAcC GLP-1R increases palatability. Because NAcC Ex9 did not affect licking for nonnutritive saccharin (0.1%), we suggest that the presence of nutrients in the gut may be required for endogenous stimulation of NAcC GLP-1R. Consistent with this, we also found that the meal size-suppressive effects of intragastric nutrient infusion were attenuated by NAcC delivery of Ex9 at a dose that had no effect when delivered alone. Analysis of licking patterns revealed that NAcC Ex9 did not reverse intragastric nutrient-induced suppression of burst number but rather blunted the effect of nutrient infusion on meal size primarily by increasing the size and duration of licking bursts. Together, our results suggest that NAcC Ex9 influences taste evaluation. We conclude that GLP-1 released in NAcC in response to gastrointestinal nutrients reduces the hedonic value of food.

Rikkunshito, an Herbal Medicine, Suppresses Cisplatin-Induced Anorexia in Rats Via 5-HT2 Receptor Antagonism

Chemotherapy with an anticancer agent generally causes gastrointestinal tract disorders such as vomiting and anorexia, but the mechanism remains unclear. Rikkunshito, a kampo preparation, is known to alleviate such adverse reactions. In this study, we attempted to clarify the mechanism. We investigated the decreases of plasma acylated-ghrelin level and food intake caused by cisplatin, serotonin (5-HT), 5-HT agonists, and vagotomy as well as the decrease-suppressing effects of rikkunshito and 5-HT antagonists. In addition, binding affinities of rikkunshito components were determined in receptor-binding assays using 5-HT2B and 5-HT2C receptors. Cisplatin, 5-HT, BW723C86 (5-HT2B-receptor agonist), and m-chlorophenylpiperazine HCl (5-HT2C agonist) markedly decreased plasma acylated-ghrelin levels, although 5-HT3 and 5-HT4 agonists had no effect. In contrast, 5-HT2B and 5-HT2C antagonists suppressed the cisplatin-induced decrease of plasma acylated-ghrelin level and food intake. Administration of rat ghrelin improved the cisplatin-induced decrease in food intake. Vagotomy decreased the plasma acylated-ghrelin level, which was decreased further by cisplatin. Rikkunshito suppressed such cisplatin-induced decreases of plasma acylated-ghrelin level and food intake. The suppressive effect of rikkunshito was blocked by a ghrelin antagonist. Components of rikkunshito, 3,3',4',5,6,7,8-heptamethoxyflavone, hesperidin, and iso-liquiritigenin showed a 5-HT2B-antagonistic effect in vitro, and oral administration of rikkunshito suppressed the cisplatin-induced decrease in the plasma acylated-ghrelin level. The cisplatin-induced decreases of the plasma acylated-ghrelin level and food intake are mediated by 5-HT2B/2C receptors and suppressed by flavonoids in rikkunshito.

Food, water and NaCl consumption by 14 strains of rats.

We measured the voluntary intake of food, water, and NaCl by 8 male and 8 female rats from each of 3 outbred strains (Crl:CD(SD) IGS, LE, and Wistar) and 11 inbred strains (BN/SsNHsdMcwiCrl, BUF/CrCrl, COP/CrCrl, DA/OlaHsd, DahlSS/JrHsdMcwi, F344/NTac, FHH/EurMcwi, LEW/NHsd, Noble/CrCrl, PVG/OlaHsd, and SHR/NCrl). At 8-week old when tests began, there was a 182-g range in body weight (PVG-female=121±2 g, LE-male=303±4 g), a 17-g range in food intake (BN-female=11±1 g/d, SHR-male=28±2 g/d of AIN-76A diet), and a 34-mL range in water intake (BN-female=15±1 mL/d, FHH-male=49±4 mL/d of deionized water). In a series of 48-h two-bottle tests with a choice between water and progressively increasing concentrations of NaCl, all rat strains strongly preferred 3.16, 10, 31.6, and 100 mM NaCl relative to water. All except BUF, Noble and PVG preferred 178 mM NaCl relative to water. All except LEW, SHR, and DA avoided 316 mM NaCl, and all avoided 562 mM NaCl. There were few differences in NaCl preference between the sexes at any concentration. These results illustrate the substantial diversity of voluntary ingestive behavior in rats and set the stage for future genetic analyses.

A role for β-melanocyte-stimulating hormone in human body-weight regulation

Pro-opiomelanocortin (POMC) expressing neurons mediate the regulation of orexigenic drive by peripheral hormones such as leptin, cholecystokinin, ghrelin, and insulin. Most research effort has focused on alpha-melanocyte-stimulating hormone (alpha-MSH) as the predominant POMC-derived neuropeptide in the central regulation of human energy balance and body weight. Here we report a missense mutation within the coding region of the POMC-derived peptide beta-MSH (Y5C-beta-MSH) and its association with early-onset human obesity. In vitro and in vivo data as well as postmortem human brain studies indicate that the POMC-derived neuropeptide beta-MSH plays a critical role in the hypothalamic control of body weight in humans.

Hypothalamic and Amygdalar Neuronal Responses to Various Tastant Solutions during Ingestive Behavior in Rats

The forebrain, including the amygdala (AM) and hypothalamus, may be a higher brain center that modulates the activity of a brainstem neural system that influences ingestive behavior via descending projections. In this study, to elucidate the characteristics of sensory information processing in the forebrain in relation to this putative connection, we recorded neuronal activity in the AM and hypothalamus [lateral hypothalamic area (LHA), medial hypothalamic area (MHA)] of rats during discrimination of conditioned sensory stimuli and the ingestion of various tastant solutions. Of 420 responsive AM neurons identified, 24 were taste responsive and located mainly in the central nucleus of the AM. Multivariate analyses of these taste neurons suggested that in the AM, taste quality is processed on the basis of palatability. In the hypothalamus, of 282 LHA and MHA neurons recorded, 144 responded to one or more conditioned auditory stimuli and/or licking of one or more solutions. Stress, which is known to influence feeding behavior, increased the mean spontaneous activity of LHA neurons but decreased the mean spontaneous neuronal activity of MHA neurons. This pattern of changes in spontaneous neuronal activity correlated with alterations in feeding behavior during stress. Furthermore, the activity of both AM and LHA neurons was modulated flexibly during conditioned associative learning. Together, the data suggest that the activity of the AM and hypothalamic neurons is altered when animals must modulate ingestive behavior by learning a new stimulus associated with food and by being exposed to stress, suggesting that these forebrain areas are important modulators of the activity of a basic neural system in the brainstem that influences ingestive behavior.

CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions.

Male rats were injected with 6-hydroxydopamine in the lateral hypothalamus and tested for ingestive behavior starting on the day after the injection. The rats did not eat food pellets but readily ingested an intraorally infused nutritive solution. If given three daily intraoral infusions, 6-hydroxydopamine-treated rats defended their body weight and were as sensitive to the inhibitory effect of cholecystokinin octapeptide on intake as controls. Dopamine was reduced by 94% in the dorsal striatum five days after the 6-hydroxydopamine injection. Noradrenaline and serotonin were less markedly affected. Thus, while appetitive ingestive behavior is disrupted, consummatory ingestive behavior and body weight regulatory competence are only marginally affected by massive damage to forebrain dopamine neural networks.

Differential effects of dorsomedial medulla lesion size on ingestive behavior in rats.

Previous studies indicate that rats with lesions centered on the area postrema (AP) drink more saline and consume abnormally large amounts of water after treatment with subcutaneous isoproterenol (Iso) angiotensin II. In addition, lesioned rats lose a significant amount of body weight immediately after surgery. Nonetheless, there are disparate reports on the effects of lesions of the AP on fluid intake and body weight. These reports suggest that the adjacent nucleus of the solitary tract (NTS) may play a role in the effects observed subsequent to the lesion. In this study we evaluated the effects of varying lesion size on body weight, fluid intake, and the baroreflex. As the lesion included more of the NTS, the effect on body weight was reduced. Moreover, water intake induced by Iso increased as more NTS was involved in the lesion. Conversely, 3-h ad libitum saline intake and saline intake after sodium depletion decreased with more involvement of the NTS in the lesion. These data suggest that the neural population in the NTS bordering the AP may play a critical role in the control of water and saline intake as well as the regulation of body weight.

Influence of peritoneal dialysis solutions with glucose and amino acids on ingestive behavior in rats

Continuous ambulatory peritoneal dialysis (CAPD) is often associated with malnutrition; reduced intake of nutrients due to anorexia is an important factor. The glucose load from glucose-based peritoneal dialysis (PD) solutions and amino acids from amino acid-based solutions may favor suppression of the appetite. To study this matter we used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery they were tested under standardized conditions by giving them an intraoral infusion (1 ml/min) of a solution containing 342 g/liter of the sucrose or 97 g/liter protein solutions while recording the time (volume) of ingestion. Control rats consumed 18.8 +/- 0.9 ml of the sucrose and 39.8 +/- 0.8 ml of the protein solutions. Injections of PD solutions with 13.6, 22.7, and 38.6 g/liter of glucose reduced the ingestion of sucrose by 12.4%, 23.6% and 36.1%, respectively, but did not affect the ingestion of protein. Injections of 30 ml of PD solutions containing 11, 18 and 31 g/liter of amino acids reduced the ingestion of both sucrose by 9.7%, 17.1% and 33.2% and of protein by 13.5%, 25.9% and 33.1%, respectively. We conclude that in our experimental model, the inhibition of appetite caused by peritoneal solutions containing glucose or amino acids seems to be specific for each nutritional constituent and not simply an effect of hyperosmolality or large filling volumes.

Bombesin and cholecystokinin differentially affect ingestive microstructural variables whether given alone or in combination.

The ability of dose combinations of cholecystokinin (CCK) and bombesin to inhibit liquid glucose (0.125 gm/ml) intake and affect microstructural components of ingestive behavior in rats was examined. Five minutes before access to the glucose solution, rats were injected with dose pairs of CCK and bombesin. Both CCK and bombesin inhibited intake in a dose-related fashion. The magnitude of the inhibition produced by dose combinations was never greater than the sum of the inhibitions produced by the individual doses. CCK and bombesin affected different microstructural components of ingestion. CCK reduced burst size and cluster size, whereas bombesin reduced burst number and cluster number. These effects of the 2 peptides were not altered by the presence of the other peptide. These results suggest that different mechanisms of action underlie the feeding inhibitory actions of the 2 peptides.

Interaction between orosensory and postingestional stimulation in the control of corn oil intake by rats

The microstructure of the ingestive behavior of rats ingesting corn oil emulsions was analyzed to describe quantitatively how postingestional stimulation interacts with orosensory stimulation to control the intake of corn oil. Seventeen hour food deprived rats were given 30-min access intake tests with corn oil emulsions ranging in concentration from 0.125% to 64%. The volume ingested showed an inverted U shaped function over this concentration range. The Weibull function fitted to the rate of licking function showed that the initial rate of licking was an increasing linear function of the log of the concentration of corn oil. The slope of the licking rate function was an increasing curvilinear function of the log of corn oil concentration. Together these results indicate that the negative feedback effect of corn oil in the gastrointestinal tract increases more rapidly at the higher concentrations of corn oil than does its orosensory stimulating effect resulting in a decrease in the volume ingested. Unlike carbohydrates, where the increase in the initial rate of licking is a result of an increase in the size of the clusters, the increase with concentration in the initial rate of ingesting corn oil was caused by an increase in the number of clusters rather than their size. This study provides a quantitative analysis of the interaction between orosensory and postingestional stimulation, two variables that play an important role in the control of ingestion of corn oil.

Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive behavior of rats.

Intact and abdominally vagotomized rats were offered for ingestion during a 30-min period a saccharin and glucose solution or another with 0.1 M mannitol added. The addition of mannitol to the test solution caused a large reduction in intake of intact rats caused by a very rapid decline in the rate of licking during the test. This did not occur with the vagotomized rats. This demonstrates that abdominal vagal nerves are necessary for the inhibitory effect of mannitol on the ingestive behavior of rats. Vagotomized rats also differed from the intact ones by ingesting less of the mannitol-free solution. This was suggested to result from accelerated gastric clearance, leading to abnormally rapid stimulation of negative feedback from the small intestine conveyed to the CNS by extravagal pathways.

Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive behavior of rats.

Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive behavior of rats.

Acute effects of ethanol on ingestive behavior in rats.

The effects of acute ethanol administration on the ingestion of NaCl and food were assessed in adult rats subjected to 1-hr drinking and feeding tests 30 min after intraperitoneal administration of ethanol. Ethanol pretreatment did not induce spontaneous NaCl ingestion, but significantly potentiated angiotensin II-stimulated salt appetite, but not water intake, in a dose-dependent manner. Similarly, ethanol pretreatment significantly potentiated neuropeptide Y-stimulated food intake in nonfasted rats, but did not, by itself, cause spontaneous food ingestion. Ethanol pretreatment also significantly blunted pituitary secretion of oxytocin in response to multiple excitatory stimuli. Finally, administration of oxytocin intracerebroventricularly prevented the ethanol-induced potentiation of salt appetite elicited by angiotensin II. In view of our previous findings that central oxytocin secretion inhibits both NaCl and food intake, we propose that ethanol potentiates the ingestion of various solutes in rats, in part, by inhibiting brain-projecting oxytocinergic pathways concurrently with its well-known effects to inhibit pituitary oxytocin secretion.

Evidence that neuropeptide Y is a physiological signal for normal food intake

Neuropeptide Y is the most potent orexigenic signal known. To test the hypothesis that NPY is a physiological messenger molecule for normal food intake in rats, we studied the effects of passive immunization against endogenous NPY on cumulative daily food intake in non-fasted spontaneously feeding rats. The results show that continuous central infusion of NPY antibodies markedly suppressed the nighttime and the cumulative 24 h food intake in a dose-dependent fashion. These results support the hypothesis that NPY may be a physiological signal involved in the stimulation of ingestive behavior in rats.

Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets.

Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets.

Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets.

A microstructural analysis of the licking behavior of the rat was used to investigate the effects of total abdominal vagotomy on ingestive behavior. Vagotomy decreased the meal size of milk and 3 concentrations of sucrose. The decrease was due to an increase in the decline in the rate of licking during the meal, suggesting that negative feedback from the gastrointestinal tract was enhanced by vagotomy, perhaps because of accelerated clearance of fluid from the stomach to the intestine. No evidence was found for motor dysfunction of licking or alterations in gustatory sensitivity to the test solution. The results suggest that vagotomy enhanced the strength of an extravagally mediated negative feedback signal from the intestine and that the vagus nerve normally prevents this from occurring by regulating gastric clearance.

Additivity of taste-specific effects of sucrose and quinine: Microstructural analysis of ingestive behavior in rats.

Additivity of taste-specific effects of sucrose and quinine: Microstructural analysis of ingestive behavior in rats.

Additivity of taste-specific effects of sucrose and quinine: microstructural analysis of ingestive behavior in rats.

Effects of sweet and bitter tastes on ingestion were studied by timing licking responses. Twelve water-deprived rats were given 15-min access to sucrose (S) solutions (0.00%, 1.25%, 2.50%, and 5.00%) with and without quinine (0.01%) and to quinine (Q) solutions (0.00%, 0.0025%, 0.005%, and 0.01%) with and without sucrose (5.00%). Volume ingested and number of licks increased with S and decreased with Q. In response to S, the number of bursts increased, and interlick intervals lengthened. In response to Q, licks to ingest 1 ml of solution, burst number, and percentage of slow licks increased, and burst size decreased. When Q and S were mixed in the same solution, the pattern of ingestive responses manifested attributes of both tastes. Results suggest 2 separate, parallel systems that operate simultaneously to govern rats' licking behavior. One system expresses the effect of S on the pattern of ingestion and the other expresses the effects of Q.

Effects of sustained central infusion of bombesin (BN) or its antagonist on ingestive behavior of rats

Effects of sustained central infusion of bombesin (BN) or its antagonist on ingestive behavior of rats

Simultaneous Display of Sexual and Ingestive Behaviour by Rats

Intraoral infusion of sucrose activates consummatory ingestive behaviour in rats selectively, i.e. the rat only emits the responses used to ingest food. Activation of consummatory ingestive behaviour in this way had no effect on the subsequent display of sexual behaviour by male or female rats and vice versa. Rats infused intraorally with sucrose and presented with a sexual partner showed ingestive and sexual behaviour simultaneously. Pretreatment with cholecystokinin octapeptide inhibited the ingestion of sucrose in both males and females but had no effect on the simultaneous display of sexual behaviour. Ingestion of sucrose from a drinking spout, a test in which the rat has to emit responses to obtain food, i.e. show appetitive ingestive behaviour, was inhibited by the presentation of a sexual partner in rats of both sexes. These results show that the mechanisms controlling consummatory sexual and ingestive behaviour operate independently and that the presentation of a sexual partner inhibits appetitive ingestive behaviour. Daily intraoral infusion of sucrose reduced pellet intake in ovariectomized rats while the rats maintained their body weight. Implantation of an oestradiol-filled implant reduced body weight and inhibited daily intake of pellets but had no effect on the intake of intraorally administered sucrose. Subsequent removal of the oestradiol implant increased sucrose intake and body weight but did not have a marked effect on pellet intake. Thus, rats respond to a lowering of the set point for body weight by decreasing their intake of the least preferable kind of food and increase their intake of the most preferable kind of food in response to an elevation of the set point for body weight. Ovariectomized rats infused intraorally once daily with a highly nutritive milk diet in the absence of food pellets ingested very large amounts and reduced their intake in response to oestradiol implantation. Thus, although oestradiol can inhibit consummatory ingestive behaviour, its suppressive effect on ingestion cannot be described in terms of selective effects on appetitive and/or consummatory aspects of the behaviour nor in terms of an alteration in the preference for a sweet solution. Inhibition of ingestive behaviour occurred within 24 h after oestrogen treatment as opposed to stimulation of sexual behaviour which had a longer latency, suggesting that oestradiol affects ingestive and sexual behaviour via different mechanisms. While the mechanisms controlling consummatory ingestive and sexual behaviour must be different, there is evidence for a common mechanism mediating the incentive motivation and reward aspects of these behaviours. The mechanisms which enable rats to select between two, possibly equally rewarding courses of action, i.e. display of sexual or ingestive responses, however, are unknown.