Effects of amylin and salmon calcitonin on feeding and drinking behavior in pygmy goats

In the present study, the effects of peripherally administered amylin and of the amylin-related peptide salmon calcitonin (sCT) on food and water intake was tested for the first time in pygmy goats. In the first series of experiments, the effect of amylin on food (0.5, 1.0 and 2.0 microg/kg b.wt.) and water (2.0 microg/kg) intake was tested. In the second series of experiments, the effect of sCT on food intake (1.0 microg/kg) was tested under ad libitum feeding conditions or after 14 h food deprivation. The relationship of dose on the effect of sCT (0.1, 0.5 and 1.0 microg/kg) on food and water intake was also tested. Finally, the effect of a low dose (0.1 sCT microg/kg) on water intake was also investigated during food withdrawal. We showed for the first time an anorexigenic effect of the satiety peptide amylin (2.0 microg/kg) in ruminants, which was characterized by a reduction in meal size. In pygmy goats, the administration of the three doses of sCT induced an anorexigenic effect, which was larger and of longer duration when compared with amylin, although the anorexigenic effect of the lowest dose never reached significance. This effect was not dose dependent and was partly due to a reduction in meal size and partly to a prolongation of the interval between meals. The anorexigenic effect of sCT was accompanied by a reduced water intake, probably due to reduced prandial drinking. Furthermore, the low dose of sCT (0.1 microg/kg) was dipsogenic during food withdrawal.     

Free-feeding and free-drinking patterns of male rats following treatment with opiate kappa agonists.

Three experiments investigated the effects of PD117302 and U50,488H on the patterns of food and water intake by male rats. Experiment 1 demonstrated early dose-related suppression of food and water intake after PD117302 (0, 1.25, 2.5, 5 mg/kg). The initial suppression of drinking was followed by a sustained increase 4-12 h after drug administration. Experiment 2 demonstrated that 2.5 mg/kg PD117302 failed to increase food intake whether given at the beginning of the night (high baseline food intake) or the beginning of the day (low baseline food intake). Experiment 3 showed that 0.5 mg/kg U50,488H significantly enhanced meal size but, at doses of 0.5, 1.0, and 2.0 mg/kg, had no effect on overall food intake. U50,488H also produced delayed, dose-related increases in water intake. The results suggest kappa receptors may have limited importance in modulating ad lib food intake and demonstrate the behavioural characteristics of increased drinking after excessive urine output.     

Circadian patterns of drinking and eating in pygmy goats.

The eating and drinking patterns of pygmy goats fed ad lib and kept on a 12 h light/12 h dark cycle were recorded and analyzed. Eighty-four percent of drafts (drinking bouts) were associated with meals (feeding bouts). Only 42% of meals were associated with drafts. In the light phase meals associated with drafts were significantly larger than meals not associated with drafts, suggesting that meal size is increased by water intake around meals. Cumulative food intake was positively correlated with cumulative water intake, but the correlation was weaker during the dark phase than during the light phase. The results demonstrate that water intake in ruminants is associated with food intake, but the link between water and food intake seems to be more pronounced during the light phase than during the dark phase.     

Depression of rat feeding in familiar and novel environment by sulfated and nonsulfated cholecystokinin octapeptide

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated cholecystokinin octapeptide (CCK-8-NS) were tested on feeding by rats in familiar and novel environment. In a familiar environment only intraperitoneally (IP) administered CCK-8-SE (0.8-24 nmole/kg) could inhibit 30 min food intake of 24 hr food-deprived rats, while the same doses of CCK-8-NS IP and both octapeptides (0.8-8000 pmole/rat) intracerebroventricularly (ICV) were totally ineffective. The effects of CCK-8-SE and CCK-8-NS on feeding were also tested in a novel environment, i.e., in an open field. The parameters of exploratory activity and food intake of 24-hr food-deprived rats were recorded simultaneously during a 15-min session. After IP injection, CCK-8-SE dose-dependently depressed the food intake, and the higher doses (8.0 or 24 nmole/kg) also decreased the open field parameters, including number of approaches to food. In the novel environment, 8.0 or 24 nmole/kg IP injected CCK-8-NS also depressed the food intake, whereas the incidence of grooming was enhanced after 8.0 nmole/kg CCK-8-NS. The most effective doses of both octapeptides increased the latency to first bite. For the open field test ICV treatment was also carried out with 8, 80 or 800 pmole doses of the octapeptides, and after 80 pmole CCK-8-SE ICV the food intake was decreased, and after 80 or 800 pmole CCK-8-SE and 800 pmole CCK-8-NS the food intake/approach parameter was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine-elicited drinking in weanling and adult rats

A total of 260 male and female adult (60-70 days of age) and weanling (22-25 days of age) Sprague-Dawley derived rats were used in these experiments. Subcutaneous administration of histamine (HA) elicited drinking in a dose-dependent manner for both ages tested, although the threshold dose varied with age. A dose of 5.0 mg/kg HA elicited significant increases in water intake for adults, whereas for weanlings a dose of 20 mg/kg HA was necessary. Adult rats exhibited decreased latency to drink after all doses of HA tested, whereas for weanlings, decreased latency was evident only after doses of HA sufficient to elicit increases in water intake. Combined antagonism of H1 and H2 receptors for HA, using dexbrompheniramine and cimetidine, respectively, inhibited HA-elicited drinking in adults and weanlings. Further investigation of the ontogeny of histamine- and food-related drinking may provide a useful approach to examine the physiological mechanisms underlying fluid consumption in adult animals and as they are gradually elaborated during ontogeny.     

Meal patterns of pygmy goats fed hay and concentrate ad lib

The meal patterns of pygmy goats fed hay and pelleted concentrate ad lib were recorded and analyzed. The pygmy goats consumed 8 hay meals [6 during the light phase (= light)/2 during the dark phase (= dark)] and 10 concentrate meals (7 during light/3 during dark) during 24 hr (12 hr light/12 hr dark). Sixty-two percent of hay and 74% of concentrate intake occurred during light. Total 24-hr hay (280 g) and concentrate (264 g) intakes were similar, but concentrate was preferred during dark. Concentrate meals were smaller during light than during dark. The mean feeding rate (g/min) within meals for both hay and concentrate was higher during dark than during light. Meal size and duration of postmeal interval were positively correlated for concentrate but not for hay. No significant positive correlation was found between meal size and duration of premeal interval. Separate analysis of diurnal and nocturnal meals indicated that the postmeal correlation for concentrate was evident primarily during dark. The results demonstrate that food intake in pygmy goats shows distinct diurnal variations and suggest that food intake in ruminants is regulated from meal to meal, with different factors prevailing during light and dark.     

Chronic fluoxetine administration desensitizes the hyperglycemia but not the anorexia induced by serotonin in rats receiving fructose-enriched chow

The present study examined the effect of chronic fluoxetine administration on the feeding behavior of fructose-fed rats. Male fructose-fed rats were divided into two groups: (1) control fructose-fed rats (CFR), and (2) fructose-fed rats treated with oral fluoxetine 5 mg/kg/day for 30 days (FFR). The feeding behaviors and plasma glucose levels in response to either serotonin (5-HT, 5 mg/kg) or saline injection were studied. The results showed 5-HT increased CFR plasma glucose in a dose-dependent fashion while FFR demonstrated significantly lower responses to 5-HT stimulation. 5-HT significantly increased the feeding latency and decreased the amount of food intake in the CFR. Fluoxetine treatment did not affect the 5-HT effect on food intake amount but significantly reduced the 5-HT effect on feeding latency. Putting the animals in a new environment increased the 5-HT effect on feeding latency further; the effect was ameliorated in the FFR. In conclusion, 5-HT induced hyperglycemia, increased feeding latency and decreased food intake amount in fructose-fed rats. Chronic administration of fluoxetine counteracted the 5-HT effects on blood glucose level and feeding latency, but not on the amount of food intake.     

Verapamil and indomethacin attenuate endotoxin-induced anorexia

To characterize the mechanism of the anorexia during infection, we investigated the effect of E. coli lipopolysaccharide (LPS) on feeding in rats under various conditions: LPS (125, 100, 75, and 50 micrograms/kg body weight = b. wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. The Ca++-channel blocker verapamil (5 mg/kg b. wt., IP) or the antipyretic and antiphlogistic drug indomethacin (2.5 mg/kg b. wt., IP), but not combined alpha- and beta-adrenergic receptor blockade by IP phentolamine plus propranolol (500 micrograms/kg b. wt., each) attenuated the anorectic effect of LPS (125 or 100 micrograms/kg b. wt.). The results suggest that a phospholipase A2-sensitive mechanism contributes to the anorexia during injection.     

Opiate antagonists and agonists and feeding in sheep

Recent evidence indicates that endogenous opiate peptides may be involved in the control of food intake. In previous experiments, injection of β-endorphin has stimulated food intake and peripheral injections of the opiate antagonist, naloxone, decreased food intake in rats. In the present experiments, food and water intakes of sheep were measured in response to peripherally administered opiate antagonists and continuous lateral ventricular administration of opiate agonists. Intravenous injections of both of the opiate antagonists naloxone (0.03, 0.062 and 0.125 mg/kg) and 3–4(hydroxyl-phenyl)-3-4-dimethyl-piperidine propiophenone maleate (0.03, 0.062 and 0.125 mg/kg) decreased food intake for up to 90 min in 4-hr fasted sheep. In water-deprived sheep, naloxone did not affect water intake or body temperature for the first 4 hr but depressed 24 hr water intake. Continuous 90-min injection of 26, 51 and 102 nmoles/min of the opiate agonist D-ala²-met-enkephalinamide (DME) increased food intake of satiated sheep. Intravenous injection of 0.125 mg/kg naloxone blocked the increase in food intake elicited by intraventricular injection of DME. In contrast, intraventricular injection of kyotorphin, a releasor of endogenous enkephalin in the brain, did not affect food intake. Thus, in sheep intracerebroventricular administration of opiate agonists increased food intake; peripheral administration of opiate antagonists decreased food intake and blocked the feeding induced by agonists.     

Increases in plasma glycerol levels precede the hypophagia following subcutaneous glycerol injection in rats

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

Comparison of the effects of bacterial lipopolysaccharide and muramyl dipeptide on food intake

For further characterization of the mechanism involved in the anorexia during bacterial infection, we investigated whether muramyl dipeptide (MDP), the minimal immunologically active structure of gram-positive bacterial cell walls, affects rats' food intake in the same way as lipopolysaccharide (LPS) from E. coli. MDP (1.6 mg/kg body weight = b.wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. Indomethacin (2.5 mg/kg b.wt., IP) but not verapamil (5 mg/kg b.wt., IP) attenuated the hypophagic effect of MDP. In further experiments, MDP and LPS (100 micrograms/kg b.wt., IP) both inhibited gastric emptying and indomethacin failed to block this effect of LPS. Hepatic vagotomy did not attenuate the hypophagic effects of MDP or LPS. LPS reduced water intake only when food was available, but reduced food intake also during water deprivation. MDP did not affect water intake. MDP and LPS both had an aversive effect, but LiCl, which was also aversive, failed to reduce feeding under the conditions tested. This questions the role of a conditioned taste aversion in the hypophagia induced by MDP or LPS. The results suggest that a stimulation of eicosanoid synthesis contributes to MDP-induced hypophagia and may therefore also contribute to the anorexia during infection. In contrast, an inhibition of gastric emptying, an activation of hepatic satiety signals or a reduction of water intake, does not seem to be crucial for the hypophagic effects of MDP or LPS.     

Enhancement or loss of the hypophagic effect of interleukin-1 upon chronic administration.

To further characterize the effect of interleukin-1 on food intake, we tested whether a tolerance to the hypophagic effect of recombinant human interleukin-1 beta (rhIL-1 beta) develops with repeated injections or continuous infusion in rats. Daily intraperitoneal (IP) injections of rhIL-1 beta (25,000 LAF units/kg b.wt.) for 4 days did not result in tolerance to rhIL-1 beta's hypophagic effect. The hypophagic effect of the same dose of rhIL-1 beta actually increased if injections were given every second day, when the hypophagic effect of the preceding injection had subsided. A dose of rhIL-1 beta that usually did not affect food intake (5000 LAF units/kg b.wt.) reduced food intake if injected repeatedly. Continuous infusion of rhIL-1 beta (25,000 LAF units/kg b.wt/day) via IP-implanted osmotic minipumps caused a strong initial suppression of feeding followed by the development of tolerance to the hypophagic effect of the infused rhIL-1 beta. Nevertheless, hypophagia caused by a subsequent IP injection of rhIL-1 beta (25,000 LAF units/kg b.wt.) was enhanced. As specific antibodies to rhIL-1 beta could be detected in sera of only three of 11 rhIL-1 beta-infused rats, the observed tolerance was probably not due to a humoral immune response. The results demonstrate that, dependent on test conditions, chronic administration of rhIL-1 beta in the rat can lead to an enhancement or to a loss of its hypophagic effect. The reasons for this difference remain unclear.     

Endogenous sugar acid derivative acting as a feeding suppressant

Evidence suggests that endogenous sugar acids 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA) may participate in the regulation of feeding. To study the effect of 2-buten-4-olide, a 2-DTA synthetic derivative, on food intake, male Wistar rats were subjected to various applications. Intraperitoneal administration of 2-buten-4-olide in doses of 30 to 100 mg/kg, decreased food intake dose-dependently by reducing meal frequency, meal size and eating rate, and prolonging meal duration, latency to eat the first meal after injection and post-prandial intermeal intervals. Drinking patterns and locomotor activity were not significantly affected. Administration of 2-buten-4-olide intragastrically in doses of 50 to 300 mg/kg, and intra-third cerebroventricularly in doses of 1.2 to 5.0 mumol/rat, dose-dependently reduced food intake. This and previous evidence suggest that: 2-DTA and its derivatives that share its bioactive components suppress food intake in the rat; They might represent a new category of potential therapeutic agents for hyperphagia and obesity.     

Further characterization of the anorexic action of orally-administered THIP, a GABA-analogue, in the rat

Sprague-Dawley rats were used to further characterize the anorexic action of orally-administered THIP, a GABA-analogue. The anorexic action of THIP (5 or 10 mg/kg) was antagonized by prior subcutaneous injection of bicuculline (1 mg/kg), but not by prior subcutaneous injection of bicuculline-methobromide (1.5 mg/kg), strychnine-SO4 (0.75 mg/kg), pentylenetetrazol (25 mg/kg), or picrotoxin (1 mg/kg). Orally-administered GABA (50-300 mg/kg), bicuculline (1-10 mg/kg) or picrotoxin (1-10 mg/kg) generally did not inhibit food intake. These results indicate that the anorexic action of THIP is mediated by central GABA-receptors.     

Further evidence for the existence of an "organismic" set point in rats with dorsomedial hypothalamic nucleus lesions (DMNL rats): normal catch-up growth

The present study was performed to assess the capacity of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) and sham-operated controls (CON) for catch-up growth following body weight (b.wt.) reduction prior to DMNL (and sham-lesion) production. Male SD rats (45 days, 157 +/- 1.3 g) were maintained for 11 days ad lib (ADLIB) after arrival and then divided into two groups. One group continued to feed ADLIB, the other group was fed half of the ration eaten by ADLIB rats for 32 days. At this point each group was divided into two subgroups. One subgroup received DMNL, the other subgroup consisted of CON. From then on all rats were fed ADLIB [except for one group of CON that was pair-fed to the ADLIB DMNL rats (PF-CON)] for 37 days (69th day of experiment) and then killed. DMNL rats lesioned at normal b.wt. (ADLIB DMNL) showed a precipitous drop in food intake, b.wt. and efficiency of food utilization (EFU). In striking contrast, rats that had received DMNL after b.wt. restriction (REST DMNL) and were then refed ADLIB showed a dramatic rise in food intake, b.wt., change in b.wt. and EFU, the latter being almost twice that of the ADLIB DMNL. Notably, the PF-CON weighed less than the ADLIB CON and utilized food poorer than ADLIB CON, REST CON and ADLIB DMNL. Liver weight (both absolute and relative (per kg 3/4 b.wt.) was reduced in DMNL irrespective of dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxytocin inhibits food and fluid intake in rats

Increasing evidence indirectly suggests a role for oxytocinergic neurons in the control of ingestive behaviors. The present study was aimed at directly investigating a possible effect of oxytocin on food and water intake in rats. Oxytocin, whether administered intracerebroventricularly (ICV) (1-10 micrograms/rat) or intraperitoneally (IP) (375-3,000 micrograms/kg) dose dependently inhibited food intake in freely feeding animals; in schedule-fed animals fasting for 21 h, oxytocin not only reduced food intake but also reduced the time spent eating and increased the latency to first meal. On the other hand, oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]-vasotocin, ICV injected at the dose of 10 micrograms/rat, increased food intake and time spent eating and reduced the latency to first meal; moreover, it completely prevented the effect of oxytocin. Water intake was studied both in freely drinking animals and in three different models of thirst (water deprivation, hypertonic saline administration, angiotensin II injection). In all cases, oxytocin dose dependently inhibited water intake, in a dose range of 0.1-10 micrograms/rat (ICV) or 93-750 micrograms/kg (IP). In the water deprivation model, ICV pretreatment with d(CH2)5Tyr(Me)-[Orn8]-vasotocin completely prevented the antidipsogenic effect of oxytocin. In conclusion, these data show that oxytocin directly inhibits food and water intake in rats, the effect being specifically mediated by brain oxytocin receptors. This may support the idea that the brain oxytocinergic system plays an important role in the regulation of ingestive behaviors.     

Feeding behavior in growing rats fed diets containing sorbose

The effect of dietary sorbose on food and water consumption was investigated in growing rats. Rats (26-day old) were fed diets containing 0, 100, 200 or 300 g sorbose/kg diet for 5 weeks in Experiment 1. Daily food and water intakes were measured at day 0, 7, 14, 21, 28 and 35. Absolute food intake (g) until day 21 decreased linearly with increasing sorbose levels and so did relative food intake (g/100 g b.wt.) until day 7. In contrast, relative water intake (ml/100 g b.wt.) and water:food intake ratio (ml/g) remained high by day 7 with increasing sorbose levels. In Experiment 2, the effect of sorbose on the short-term food intake was compared with those of glucose, sucrose and maltitol in growing rats (25-day old) at a level of 100 g/kg diet in order to investigate how quickly reduced food intake would be induced by sorbose consumption. Cumulative food intake was determined every hour for the first ten hours, then at two-hour intervals thereafter during the 24-hour period that followed feeding. As rapid as 6 hours after feeding, cumulative food intake significantly decreased in sorbose-fed animals compared with other dietary groups. It was concluded that sorbose consumption decreased the food intake of growing rats from 6 hours to a few weeks after feeding, but this inhibitory effect disappeared afterwards.     

RNA content of neurons in the ventromedial nuclei and lateral hypothalamic area relative to feeding status

The total RNA content of hypothalamic and cortex neurons in relation to the feeding status of adult male Wistar rats was studied. Experimental conditions including food deprivation (12 and 24 hours) and relative satiation (short-term refeeding, glucose or glycerol administration) changed in different ways the total RNA content of the neurons in the ventromedial hypothalamic nuclei (VMH) and in the lateral hypothalamic area (LHA) with respect to fasting or satiety. Only the long-term absence of food (24 hours) significantly increased the total RNA content of the VMH cells, while the RNA content of the LHA neurons significantly decreased in both the 12 and 24 hr fasted rats compared with those fed ad lib. The sixty minute free access to food after 12 or 24 hours of fasting fully reversed these changes. The short-term food intake significantly increased the RNA content of the LHA cells of the 12 and 24 hr fasted animals while the total RNA content of the VMH neurons significantly decreased only in the 24 hr fasted rats. The effect of glucose and glycerol administration on the RNA content of the LHA neurons (in 12 hr fasted rats) was similar to the effect of refeeding. One hour after giving glucose (1 g/kg b.wt.) or glycerol (300 mg/kg b.wt.) the total RNA content in the LHA neurons significantly increased. No changes in RNA content were observed in the neurons of the cortex when comparing the experimental and control rats. The results demonstrated the close relationship between the RNA content of the hypothalamic neurons and the feeding status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine plays a major role for drinking elicited by spontaneous eating in rats

The effects of combined antagonism of H, (using 1 mg/kg dexbrompheniramine IP) and H₂ (using 16 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 1-hr water deprivation, and (c) drinking during spontaneous eating were examined at 1 hr into the dark phase of a 12:12′-hr light/dark cycle for 14 Sprague-Dawley male rats. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without affecting drinking after water deprivation. Histaminergic antagonism did not affect spontaneous eating, but it appeared to abolish drinking prior to a meal (for only those 3 rats which exhibited such drinking), delayed the latency to initiate drinking after initiating a meal, and inhibited drinking which occurred during and after eating but prior to postprandial resting (i.e., satiety for food). Because antagonism of peripheral histamine receptors inhibited food-related drinking by over 60%, these results provide indirect support for the hypothesis that the preabsorptive food-contingent vagally-mediated release of gastric mucosal histamine plays a major role in spontaneous food-related drinking in the rat.     

Acute increase in food intake after intraperitoneal injection of metformin in rats

We studied the effect of intraperitoneal injection of different doses of the antihyperglycemic agent metformin on food intake and plasma metabolites (glucose, free fatty acids, beta-hydroxybutyrate) in rats fed a high-fat (HF) or a high-carbohydrate (HC) diet. Unexpectedly, metformin, at a dose of 120 mg/kg b.wt. stimulated food intake in both HF- and HC-fed rats, without affecting blood glucose level. This result is in contrast with the hitherto performed studies that found an anorectic effect of metformin in rodents. It is postulated that the hyperphagic effect of metformin might be related to reduced energy availability to hepatic metabolic sensors controlling food intake, because metformin's known inhibitory effect on oxidative phosphorylation mainly affects the hepatoportal area, and blockade of oxidative phosphorylation in this area has been shown to stimulate feeding.