Dipsogenic and feeding influences of intraventricularly infused anionic choline solutions.

Chloride and bicarbonate solutions of choline were infused into the anteroventral part of the third ventricle of two different groups of rats through chronically implanted stainless steel cannulae. Dipsogenic and feeding responses elicited by these solutions were studied by observations taken at half hour intervals up to two h and then, after 24 h of infusions. Results were compared with the control response evoked by similar infusion of artificial cerebrospinal fluid (aCSF). Food and water intakes were recorded in different groups (n = 18 each) of rats. Dipsogenic response elicited by choline chloride solution in the observation taken 24 h after infusion, however, was higher only as compared to the control. Dipsogenic effect of bicarbonate solution was not significantly different from the control in the first two observations (30 and 60 min), but in the later observations (90, 120 min and 24 h), it was significantly higher. None of the choline solutions significantly alter feeding response within 2 h of infusions. However, in the observation taken 24 h after infusion, the response evoked by choline chloride was greater than that elicited by aCSF. The results support our earlier observation that chloride concentration of third ventricular CSF significantly influences water and food consumption. Intraventricularly administered choline also appears to have positive influence on these behaviors.     

Intracerebroventricular chloride infusion enhances water intake in rats

Central anionic influences on dipsogenic response was studied in 54 euhydrated rats. Quantity of water consumed following third ventricular infusions of equimolar hypertonic chloride and bicarbonate solutions of sodium, potassium, calcium, and barium was compared. Control group (n = 6) was given artificial cerebrospinal fluid infusion while rats of the remaining 8 groups (n = 6 each) received one of the test solutions. All the chloride solutions, irrespective of the cations to which they were associated, elicited significantly greater dipsogenic response as compared to the control, or the bicarbonate solutions. Response of the bicarbonate solutions was more than the control only in the observation taken 30 min after the infusions. In the later observations, there was no significant difference. Drinking was not affected significantly by the cationic composition of the infusion fluids. Anionic concentration of the solutions has predominantly influenced the dipsogenic response. Enhancement of drinking following infusions of chloride solutions suggests the possibility of the CSF anions exerting active physiological influences over the juxtacerebroventricular sensors.     

Water drinking caused by intracerebroventricular infusions of hypertonic solutions in cattle

Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows.     

Pancreatic glucagon,food deprivation and feeding in intact and vagotomized rabbits

Thirty New Zealand female rabbits were implanted with hepatic-portal cannulas and six simultaneously underwent bilateral subdiaphragmatic vagotomy. When recovered, all animals received pancreatic glucagon infused at 1.0 cc/min for a total dosage of 12 μg in 3.0 cc of isotonic saline. On alternate days, isotonic saline alone was infused as a control. Twelve intact and six vagotomized animals received infusions terminating food deprivations of 4, 8, and 24 hr while the remaining animals received the infusions only when free feeding. The feeding behavior of all animals was measured at 0.5, 1 and 2 hr postinfusion. Glucagon significantly suppressed feeding relative to saline only in 0- and 4-hr food-deprived intact rabbits. Longer deprivations followed by glucagon did not produce suppression, and glucagon was completely ineffective in suppressing feeding in vagotomized animals. Although glucagon infusion in 4-hr food-deprived intact rabbits produced 38% suppression of food intake during the first hr postadministration, glycogen analysis revealed no significant reduction under the behavioral testing paradigm. These results indicate that glucagon can suppress food intake without depletion of liver glycogen. It is suggested that glucagon is not a satiety signal but can probably suppress feeding through initiating glycogenolysis.     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Food intake after intragastric meals of short-, medium-, or long-chain triglyceride

Food-deprived Sprague-Dawley rats were given equicaloric intragastric infusions of mixed meals consisting largely of short- (SCT), medium- (MCT), or long-chain triglyceride (LCT). When animals were allowed to feed 20 min after infusion, there was an immediate reduction of food intake that was sustained over the 2 hr feeding period. During the first hour of feeding, the SCT, which is digested and absorbed more rapidly than the MCT or the LCT, was more effective per calorie in reducing food intake than these longer-chain triglycerides. However, during the second hour, cumulative intakes after the different triglyceride infusions were not significantly different. Equicaloric infusions of the MCT and the LCT resulted in equivalent reductions of food intake at all times. The satiety effects of these two triglycerides appear to be related to their caloric properties rather than to chain length. Since the LCT reduced food intake before the absorbed fat could have entered the blood to stimulate satiety·signals, this satiety effect may be mediated by a gastroenteric signal. None of the triglyceride infusions resulted in a conditioned taste aversion suggesting that food intake was reduced through normal satiety rather than through discomfort.     

The satiety effects of intragastric macronutrient infusions in fatty and lean Zucker rats

To evaluate satiety in the hyperphagic, genetically obese Zucker “fatty” (fafa) rat, food-deprived fatty and lean (FaFa) control rats were given equicaloric intragastric infusions consisting largely of fat, carbohydrate, or protein. Relative to distilled water infusion, these infusions resulted in immediate reductions of food intake in both fatty and lean rats allowed to feed 20 min post-infusion. Cumulative food intakes remained reduced throughout the 2 hr period of observation. Thus, despite its hyperphagia, the fatty rat is responsive to the satiating effect of infused nutrients. However, the relative satiating effectiveness of the macronutrient infusions differed for the two genotypes. In lean rats, the different macronutrient infusions resulted in equivalent reductions of feeding. In contrast, in fatty rats, fat was the least satiating and protein was the most satiating macronutrient. Moreover, compared to lean rats, fatty rats displayed less initial suppression of feeding after fat infusion and greater overall suppression after protein infusion. These effects are consistent with the long-term feeding behavior of the fatty rat for the different macronutrients and may be related to pre- and postabsorptive metabolic alterations that have been documented in this animal.     

Cholecystokinin interacts with pregastric food stimulation to elicit satiety in the rat

Rats were equipped with chronic gastric fistulas to permit sham feeding of a liquid food. After 17 hr of food deprivation, rats were injected with the intestinal hormone cholecystokinin (CCK, 40 U/kg) at various times before and after the onset of sham feeding. CCK interacted synergistically with the pregastric food contingent stimuli of sham feeding: When injected 12 min before sham feeding began, CCK suppressed sham feeding less than when injected 6 min before, at the onset or 6 min after sham feeding began. CCK suppressed sham feeding most when injected 12 min after sham feeding began. This synergism for satiation is very similar to that observed in previous experiments of identical design that investigated the interaction between the pregastric food contingent stimuli of sham feeding and the satiety effect of duodenal infusions of liquid food. The similar synergism between sham feeding and CCK or intestinal food is consistent with our hypothesis that CCK mediates the satiety effect of food in the intestine in the rat.     

Light-dark patterns in running-wheel activity in rats during chronic administration of theophylline

Running-wheel activity for 24 hr and activity patterns were studied during chronic theophylline administration. Theophylline altered the normal relations between activity level and illumination. Dark-time activity was decreased to approximately 50% and 24 hr activity was unaffected. These observations were consistent with previous results showing that theophylline suppressed dark-time feeding but had no effect on 24 hr food intake. A possible mechanism to account for these results may be dependent on levels and turnover of brain norepinephrine.     

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions

Infusing conscious unrestrained rats with either 0.5 M NaCl-CSF or 0.7 M sucrose-CSF into the lateral cerebral ventricle (IVT) at 38 microliters/hr for 4 hr induced drinking. Although the infusates were nearly equiosmotic, water drinking during the 0.5 M NaCl-CSF was greater than during 0.7 M sucrose-CSF. However, IVT infusions of 0.7 M mannitol-CSF at rates of 9.4 microliters/hr or 38 microliters/hr for 4 hr or 10 microliters/hr for 4 days failed to induce water drinking. Also, IVT infusion of 0.27 M mannitol-CSF at 38 microliters/hr for 4 hr failed to significantly alter water drinking. CSF [Na] was reduced by IVT infusion of either 0.7 M sucrose-CSF or 0.7 M mannitol-CSF. In contrast, CSF [Na] was increased by 4-hr IVT infusion of 0.5 M NaCl in rats denied access to water during the infusion. Intake of 0.5 M NaCl was not altered significantly from control intakes by any of the above IVT infusions. It is concluded that water drinking in the rat may be initiated by stimulation of either a sodium sensitive sensor alone or with an osmoreceptor system and that species specific differences in the induction of both water drinking and hypertonic saline drinking are apparent.     

The effect of intracerebroventricular hypertonic infusion on sodium appetite in rats after peritoneal dialysis

Sixty minute peritoneal dialysis (PD) against isotonic glucose decreased sodium concentration [Na+] in serum and cerebrospinal fluid (CSF) to 14% and 7% of their initial values, respectively. About 3 to 4 hours after PD, [Na+] began to increase slowly, reaching the initial level 24 hr afterwards. Central restoration of Na+ was made by infusing isotonic or hypertonic fluid into the 3rd brain ventricle (3BV) of rats at different times after dialysis. Continuous infusion (1 microliter/hr) of artCSF, 150 mM Na+, from -1 to 24 hr after PD decreased sodium intake as compared with uninfused control or control receiving Na+-free infusate or distilled water. Hypertonic central sodium infusions (1 microliter/hr) administered from -1 to 8 hr after PD, did not modify sodium intake; however an infusion made from 8 to 24 hr or from 16 to 24 hr post-dialysis decreased sodium intake by 38% and 67%, respectively. The volumes of sodium ingested were compared with those of the same animal infused with CSF 150 mM Na+. The results suggest that the fall in CSF [Na+] after sodium depletion by itself does not seem to be a critical factor in the onset of specific sodium appetite.     

Cerebrospinal fluid pressure of anaesthetized rats during intracerebroventricular infusion

Increases in cerebrospinal fluid pressure (CSFP) were measured in the lateral ventricle in barbiturate anaesthetized male Sprague Dawley rats during intracerebroventricular (IVT) infusions into the contralateral ventricle. IVT infusions of isotonic artificial CSF (art-CSF) solutions at 10 and 38 microliters/hr increased mean CSFP from control preinfusion level of 3.6 cm H2O to 4.6 cm H20 (n.s.) and 5.2 cm H2O (p less than 0.01) respectively with CSFP appearing to attain equilibrium after 30-60 min of infusion. IVT infusion of hyperosmolar art CSF solutions (saccharide and salt solutions of approximate 1000 mOsm/kg) at 38 microliters/hr resulted in a larger increase of CSFP which equilibrated at 8.5 cm H2O (p less than 0.001) after 90 min of infusion. It is suggested that on the basis of CSFP measurements in these and other experiments cited that IVT infusions be run at infusion rates of less than 40 microliters/hr to ensure minimal physiological change.     

Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCl and water deprivation in sheep

Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i.c.v.) and intracarotid infusions of hypertonic NaCl solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i.c.v. NaCl were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCl. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i.c.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCl. The thirst-eliciting infusions of hypertonic NaCl into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i.c.v. non-dipsogenic 'control' infusion of a slightly hypertonic (0.154 M) NaCl solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i.c.v. and intracarotid infusions of hypertonic NaCl. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCl. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst-eliciting effect of intravascular infusion of hypertonic NaCl may be induced without concomitant increase in CSF [Na] and/or osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Paradoxical stimulation of food intake by larger loads of glucose,fructose and mannose: Evidence for a positive feedback effect

The phenomenon of paradoxical stimulation of food intake by larger alimentary loads of isotonic glucose was studied with regard to a variety of experimental and nutritional conditions. Thus, paradoxical feeding response was induced not only by the infusions of glucose but also of the other insulinogenic sugars—fructose and mannose. Stimulation of food intake was further observed following the administration of larger volumes of isotonic glucose solutions via the duodenal and intraperitoneal infusion routes in free feeding as well as in 12 hr food-deprived animals. This paradoxical alimentary response was not eliminated or reduced by repeating these infusions daily over a longer period of time; in fact, food in the first postinfusions hour and, unexpectedly, also the total daily food intakes, showed a gradually increasing trend with daily repetitions. Drinking of isotonic glucose for 1 hr in 12 hr water-deprived animals did not suppress the subsequent intake of regular food despite the substantial amount of glucose drunk (94.1 ml vs 76.5 ml of water in controls during the same time period). The conbination of glucose drinking with subsequent food intake resulted in a significant caloric imbalance during the first hour which was not fully compensated within the 24 hr. These findings indicate that larger loads of insulinogenic sugar loads are capable of triggering an antiregulatory positive feedback alimentary response which can induce caloric imbalance and thus adversely affects the short-term maintenance of energy balance.     

Short-chain polyhydroxymonocarboxylic acids as physiological signals for food intake

In order to clarify the effects of endogenous organic acids on short and long-term feeding behavior, ingestive behavior was monitored for 2 hr before and after intra-third ventricular infusions of 3,4-dihydroxybutyric acid (2-deoxytetronic acid, 2-DTA), 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), and 3-hydroxybutyric acid (3-HBA). In addition, meal patterns were recorded for 2 days before and after the ventricular infusions. 2-DTA suppressed both short and long-term feeding by decreasing meal size (MS). 3-DPA elicited transient feeding behavior, but caused no change in long-term feeding. 3-HBA initially stimulated feeding, but subsequently suppressed long-term feeding by decreasing MS and prolonging postprandial intermeal interval (IMI). The suppressive effects of 3-HBA on feeding behavior lasted about 24 hr longer than those of 2-DTA. Based upon these observations as well as our previous reports, it appears that some of the processes affecting hunger and satiation are mediated by changes in central and peripheral concentrations of these organic acids.     

Transient vasopressin release and thirst in response to prolonged intracerebroventricular infusions of hypertonic mannitol in saline

In the conscious goat infusions of 0.4 M mannitol in 0.15 M NaCl into the lateral cerebral ventricle (40 or 100 min, 0.02 ml/min) caused slight, transient vasopressin release and temporary thirst, whereas infusions or pure, hypertonic (0.7 M) mannitol did not elicit thirst and inhibited the basic vasopressin release in the nonhydrated animal. In contrast, infusions of equiosmolal (0.35 M) NaCl induced persistent thirst and pronounced elevation of the plasma vasopressin concentration throughout the infusion period. The cerebrospinal fluid (CSF) osmolality was raised by the same order of magnitude (= 13%) after the mannitol/NaCl and the hypertonic NaCl infusions. The CSF Na+ concentration was elevated by greater than 10% at 5 min after hypertonic NaCl infusions, but it was reduced by approximately 10% at 5 min after the mannitol/NaCl infusions. There was no appreciable difference in the CSF K+ concentration after the infusions. The results are discussed with regard to the possible importance of CSF Na+-concentration as opposed to strict osmotic factors for the excitation of receptors involved in the control of water balance.     

Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCI and water deprivation in sheep

Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i. e.v.) and intracarotid infusions of hypertonic NaCI solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i. e.v. NaCI were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCI. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i. e.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCI. The thirst-eliciting infusions of hypertonic NaCI into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i. e. v. non-dipsogenic ‘control’ infusion of a slightly hypertonic (0.154 _M) NaCI solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i. e.v. and intracarotid infusions of hypertonic NaCI. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCI. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst-eliciting effect of intravascular infusion of hypertonic NaCI may be induced without concomitant increase in CSF [Na] and/or osmolality. A simultaneous increase in CSF and plasma [Na] and/or osmolality is suggested to contribute to the conspicuous water consumption seen in response to dehydration compared to that caused by acute administration of hypertonic NaCl.     

Dipsogenic Effects of Intracarotid Infusions of Various Hyperosmolal Solutions

Thirst in response to intracarotid and intravenous infusions (1.5 ml/min) of various hypertonic, equi-osmolal solutions was studied in the goat. Intracarotid infusions of 1 M NaCl and of 2 M fructose induced conspicuous cumulative drinking. The amount of water drunk during intracarotid infusions of 2 M urea and glycerol was only about a third of that consumed during the corresponding infusions of NaCl and fructose. During intracarotid infusions of 2 M galactose and glucose drinking was inconsistent. Of the intravenous infusions only hypertonic NaCl had a consistent dipsogenic effect. However, the amount of water consumed was considerably smaller and the latency time for drinking much longer than during the intracarotid infusions of NaCI. It is concluded that intracarotid infusions of hypertonic solutions act as considerably stronger thirst stimuli than corresponding intravenous infusions, and that the most pronounced dipsogenic effect is obtained by intracarotid infusions of those hypertonic solutions which also most effectively release antidiuretic hormone in the hydrated goat. The possibility is discussed that intracarotid infusions may stimulate the thirst mechanism indirectly via a rise in the Na+ concentration of the cerebrospinal fluid.     

Third ventricular chloride infusions enhance drinking in water deprived rats

The influence of intraventricularly infused anions on drinking was studied in 54 water deprived male rats, divided in 9 equal groups. Stainless steel cannulae were chronically implanted into the anteroventral part of the third ventricle (AV3V) and the animals were water deprived for 24 hr prior to the infusions. Control group (n = 6) was given 10 microliters of artificial cerebrospinal fluid. The rats of the remaining 8 groups received similar quantity of equiosmolar chloride or bicarbonate solution of either sodium, potassium, calcium or barium. Cumulative quantity of water consumed in 30 min, 1 hr, and 24 hr after the infusion was recorded. All the chloride solutions, irrespective of the associated cation, enhanced drinking. Effects of the bicarbonates were relatively weak and transient. Dipsogenic effects of the solutions depended on their anionic composition. Thus, chlorides of all the cations elicited greater drinking than their bicarbonates. Responses of the similar anionic solutions were comparable. It appears that intraventricularly infused chloride ions stimulate drinking in water deprived rats.     

Characterization of central actions of neuropeptide Y on food and water intake in rabbits

The effects of a 36-amino acid peptide, neuropeptide Y (NPY), on feeding and drinking behaviors were studied in young and adult rabbits. Intraventricular injection of NPY to adult rabbits induced feeding and drinking in a dose-related manner. While the lowest doses tested (0.2 micrograms) was without effect, other doses (0.5 and 1 microgram) elicited feeding and drinking almost instantaneously. When 1, 5 and 10 microgram doses were injected into young rabbits, immediate increases in feeding and drinking were evident, but differences in the magnitude of responses among these dosages were significant only in water consumption. Unlike studies in rats, in these rabbits NPY elicited a more pronounced response in drinking than in feeding. The drinking response after NPY administration was not a consequence of food intake because it occurred in the absence of food. With ad lib feeding, the majority of enhanced food consumption was confined to the first 30-min after NPY injection; however, an increased motivation to eat was retained for at least 2 hr after NPY when food was withheld and then returned. These observations are consistent with specific stimulatory effects of NPY on food and water intake.