Behavioral and physiological aspects of body fluid homeostasis in Fischer 344 rats

Previous studies have shown that Fischer 344 rats, unlike many other strains, have neither a spontaneous preference for dilute NaCl solutions nor an excessive consumption of it after sodium depletion. The present studies examine some characteristics of water intake in Fischer 344 rats. Their spontaneous water intake was only about 50% of that of age-matched Sprague-Dawley rats, and the water-to-food ratio was about 30% lower. When water was added to the food, Fischer 344 rats decreased their fluid intake by a corresponding amount, whereas Sprague-Dawley rats continued to drink substantial amounts. In the absence of food, Fischer 344 rats reduced their water intake by a greater fraction than rats of the Sprague-Dawley strain. Physiological changes during these studies were as expected from the behavioral data, except that plasma protein concentration was consistently 10% higher in Fischer 344 rats. In contrast to this economy in their spontaneous drinking, water intakes of Fischer 344 rats were comparable to Sprague-Dawley rats in response to water deprivation, and administration of either hypertonic NaCl or angiotensin II, and in a sham-drinking paradigm. However, following treatment with either isoproterenol or polyethylene glycol, Fischer 344 rats drank considerably less than Sprague-Dawley rats. Possible reasons for, and implications of, these strain differences in drinking are discussed.     

Drinking to intracellular dehydration following vagotomy in rats

Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.     

Regulation of NaCl solution intake and gastric emptying in adrenalectomized rats

Adrenalectomized (adrex) rats adaptively increase NaCl intake to compensate for the uncontrolled loss of Na(+) in urine due to the absence of aldosterone. After a period of NaCl deprivation, they ingest saline avidly but stop drinking before hyponatremia is repaired. The present experiments determined whether pre-systemic signals inhibit further NaCl intake, and whether gastric emptying of Na(+) is modulated according to the concentration of ingested NaCl solution. After overnight deprivation, adrex rats consumed 0.05 M and 0.15 M NaCl at a maximally fast rate ( approximately 1.7 ml/min) and emptied ingested fluid from the stomach at a slower but maximally fast rate ( approximately 1.1 ml/min). When 0.30 M NaCl was consumed instead, fluid intake still was maximally fast but gastric emptying slowed in proportion to concentration so that the emptying of Na(+) was comparable to that observed when 0.15 M NaCl was ingested ( approximately 0.13 meq/min). When 0.50 M NaCl was consumed, intake slowed proportionately so that Na(+) consumption was comparable to that observed when 0.30 M NaCl was ingested ( approximately 0.5 meq/min). NaCl intake appeared to be inhibited both by the concentration of saline emptied from the stomach and by the volume of ingested fluid in the stomach and small intestine. Gastric emptying also slowed proportionately when 0.50 M NaCl was consumed, as if the rats were regulating the delivery of Na(+) to the small intestine. These results suggest that adrex rats can detect the volume and concentration of ingested NaCl solution presystematically and integrate these two variables, and thereby modulate the rates of Na(+) intake and gastric emptying.     

Rats drinking quinine- or caffeine-adulterated water defend lean body weights against caloric and osmotic stress

Adult male and female rats drank ad lib water containing as much as 0.2% quinine hydrochloride or caffeine, and ate dry food. Maintained body weights were lower in direct proportion to the concentration of adulterant. Cumulative caloric intakes and the water and fat contents of carcasses showed that the weight lost on adulterated water and regained on tap water was fat rather than fluid. Furthermore, lean rats on adulterated water ate and drank more when ambient temperature was reduced; drank more and approximately maintained caloric intake when their food contained up to 5% sodium chloride; and ate less to compensate for the caloric value of a nonhydrating liquid diet force fed by gavage. The rats also adapted to activity wheels and behaved like rats drinking tap water during and after two days of food deprivation. Thus, the percentage adulteration of obligate drinking water determines the body weights at which rats eat and drink to defend energy balance. The rats remain in water balance even though ratios of water to food intakes were depressed by one-third in males and one-half in females for concentrations of adulterant between 0.05 and 0.2%, inclusive. These results can be used to argue that standard concepts and procedures for describing motivational and physiological states are inadequate.     

Changes in salt intake after abdominal vagotomy: Evidence for hepatic sodium receptors

Several reports have suggested that the mammalian liver contains neural receptors, innervated by the vagus nerve, that monitor the sodium concentration and osmolarity of the portal circulation. These reports have been concerned primarily with either the neurophysiological identification of these receptors or their role in the short term control of urine output. Inasmuch as relatively little is known about the role of these receptors to consummatory behavior, we investigated the effects of hepatic vagotomy in rats on sodium intake as well as on sodium output. Hepatic vagotomized (HV) rats drank less NaCl solution (0.03, 0.1, 0.3M) in 24 hr during a two-bottle test with water than sham operated rats. Comparable differences in the intakes of either water, KCl or glucose solutions were not found. The two groups of rats did not differ in their intakes of water or 0.3M NaCl after an injection of either an osmotic load (IP, 2 M NaCl, 1% BW), deoxycorticosterone acetate (SC, 5 mg) along with furosemide (SC, 10 mg), or after 10 days of sodium deprivation. Urinary sodium output was reduced in HV rats during sodium deprivation but not when the rats had adequate levels of sodium in their diet. Because circadian patterns of water and food intake as well as body weight growth of hepatic vagotomized rats were similar to those of control rats, general malaise due to surgery and generalized deficits in motivation were ruled out as explanations for the depressed daily drinking of NaCl solutions. These findings support the existence of hepatic sodium receptors and their possible involvement to the control of sodium regulation.     

Saccharin drinking and mortality in rats

Rats maintained on reduced food and offered a mixture of sodium saccharin and soda bicarbonate (saccharin) or saccharin versus water drink abnormally large quantities of saccharin resulting in body weight loss and death. Animals, particularly those on higher concentrations, periodically reduce their saccharin intake. Some of those that do not do this die. Those rats which either do not drink excessive amounts, or drink less when first introduced to saccharin, and/or fluctuate their intakes tend to survive. Both components of the saccharin mixture produce these effects (Experiment 2) but the sodium saccharin and the mixture of the two bring them about more strongly (Experiments 1 and 2). All this is support for the accommodation interpretation, or a mechanism which this study has shown to develop with consumption time, and seems to enable some animals to recuperate and survive on the same or even higher saccharin concentration. Mortality seems to depend on the amount of saccharin ingested and also on the availability of food while saccharin is drunk (Experiment 3).     

Suppression of food intake in diabetic rats by voluntary consumption and intrahypothalamic injection of glucose

When given a choice between 2 concentrations of glucose (5 and 35%) normal rats prefer to consume most of their glucose from the concentrated source while diabetics prefer the dilute source. Although both consume approximately the same total amount of glucose, on a caloric basis the glucose depressed chow intake more in diabetics than in normal rats, indicating that diabetics can experience the satiating effects of glucose. Also, since the diabetics excreted more glucose in urine during the glucose access, the overall retention of calories appeared to be less than of controls, indicating the diabetics are effectively hypophagic as compared to controls when they ingested large quantities of glucose. Direct injection of glucose into the ventromedial hypothalamus suppressed feeding as effectively in diabetics as in controls, indicating that normal titers of insulin are probably not necessary for suppression of feeding by ingested glucose in diabetic animals.     

Hypertension in rats with hereditary diabetes insipidus

The effect of age, sex and salt intake on the hypertension produced in homozygous (DI) and heterozygous (non-DI) Brattleboro rats and Long Evans rats was studied. The left kidney was removed at the age of 25, 35, 50 and 80 days (UNX 25, UNX 35, UNX 50, UNX 80), and 0.6% NaCl solution or water was offered as drinking fluid. In UNX DI rats drinking saline the mean value of blood pressure (BP) exceeded 150 torr. The highest values of BP were observed in DI UNX 25 females while no hypertension occurred in rats UNX 80. There was no correlation between individual values of BP and saline consumption in DI females with hypertension. However, individual BP values correlated with the urinary Na+/K+ ratio measured in the course of 24 h of water deprivation, due to age-dependent sodium excretion the values of which were highest in the UNX 25 group. Hydronephrosis was present in all DI rats with manifest hypertension. In hypertensive animals, BP values, Na+/K+ ratio and the frequency of hydronephrosis exhibited the same age dependence. The role of age and adaptability to the increased saline intake in the susceptibility of DI rats to experimental hypertension is discussed.     

Sham drinking in rats: osmotic and volumetric manipulations

Male rats, fitted with indwelling gastric fistulas, were tested with either a closed fistula (normal drinking) or an open fistula (sham drinking) following either intracellular dehydration (with NaCl), extracellular dehydration (with PEG), or the combination of the two stimuli. In normal drinking tests, the combined stimulus induced an intake of water that was the sum of the individual effects. In sham-drinking tests, both NaCl- and PEG-treated rats drank up to twice that of their normal drinking counterparts, but those given NaCl + PEG showed no such increase. Various body fluid measurements confirmed the persistence of the respective dehydration states at the end of sham-drinking sessions. The relatively poor or absent sham drinks after these stimuli are contrasted with vigorous sham drinking following fluid deprivation. In a second experiment, sham drinking following NaCl injections did not improve with repeated testing, but intake after intravenous infusion of NaCl did show some increase but was still modest and slow compared with that after fluid deprivation.     

Age-dependent polydipsia in the SWR-J mouse

Both absolute water intakes (ml) and relative water intakes (ml/100 g body weight) increased with age in the SWR/J mouse. This age-dependent polydipsia was more pronounced in the females than in the males. The polydipsia was abolished by food deprivation and by giving a 20% sucrose solution in place of water. Intakes of polydipsic mice were elevated still further by offering 5% sucrose and 0.2% and 0.5% saccharin. The well-defined circadian rhythm of drinking in this strain was not altered by the development of polydipsia. In females, the increase in water intakes was accompanied by a decrease in intakes of isotonic and hypertonic NaCl solutions in a single tube test. It is suggested that the SWR/J mouse might provide a model for the study of behavioral changes accompanying age-dependent renal deterioration.     

Altered NaCl taste responses precede increased NaCl ingestion during Na(+) deprivation

It has been suggested that Na(+) deficiency alters the sensitivity of taste receptors, thereby rendering NaCl solutions more palatable or preferred and more likely to be ingested. Increased ingestion of concentrated NaCl solutions by rats during dietary Na(+) deprivation occurs only after approximately 8-10 days. To determine whether changes in gustatory responses mediate the deprivation-induced NaCl ingestion (salt appetite), we evaluated taste responses to a range of NaCl concentrations before, during, and after dietary Na(+) deprivation. Rats were trained to lick rapidly in short-duration (10 s) tests by mixing NaCl solutions in a dilute sucrose solution. This method elicited consistent, interpretable rates of licking, even of normally avoided NaCl concentrations, without the necessity of depriving the rats of water. The licking rate increased after dietary Na(+) deprivation of only 2 days, increased further after 5 days of Na(+) deprivation and, after 10 days, was not different from that after 2 days. These results suggest that a change in the response to NaCl taste, as evidenced by increased rates of licking during short-access tests, occurred after 2 days of dietary Na(+) deprivation. In contrast, a significant increase in the 24-h ingestion of a concentrated NaCl solution occurred only after approximately 1 week of maintenance on Na(+)-deficient chow. Thus, it is unlikely that a delayed change in the response to NaCl taste to more palatable or preferred underlies the delayed increase in 24-h NaCl intake during dietary Na(+) deprivation.     

Postingestional modulation of drinking induced in rats by angiotensin II: intragastric infusion and sham drinking studies

The dipsogenic potency of angiotensin II (ANGII, 200 micrograms/kg, SC) was examined after the removal of various postingestional factors. In the first experiment, rats with intragastric catheters were injected SC with ANGII and allowed water to drink. During the induced drinking, either NaCl (1.5 M) or water was injected into the stomach via the catheter at a rate of 0.1 ml for each ml water ingested orally. The water intake was identical in the two conditions. In a second experiment, rats, fitted with gastric fistulas, were administered ANGII and subsequent water intake with fistulas open was compared to that occurring with the fistulas closed. Rats drank more water during the first trial with fistulas open than with fistulas closed. Water intake during subsequent trials with an open fistula rose above that observed on the first trial. In a third experiment, rats with gastric fistulas were offered 0.15 M NaCl to drink. Intake was greater when the fistula was open than when it was closed. Intake of 0.15 M NaCl increased during the second trial with fistula open. Rats drank more 0.15 M NaCl during the first trial with an open fistula in Experiment 3 than those rats given water to drink on their first trial with fistula open in Experiment 2. These data suggest both oropharyngeal and postingestional factors interact in the control of ANGII-induced fluid intake.     

Water intake regulation in rats after intestinal bypass surgery

Jejunoileal bypass surgery in normal-weight female rats produced a temporary reduction in food intake, and small but more long lasting reductions in water intake and the water to food intake ratio. The bypass rats, however, did not differ from controls in their drinking response in a variety of thirst tests. That is, the bypass rats displayed normal increases in water intake following 24 hr water deprivation, hypertonic saline injection, or injection of polyethylene glycol; and normal decreases in water intake when food deprived or when given quinine-adulterated water. On the other hand, the bypass rats did not drink as much as did the controls when offered isotonic saline, or a saccharin solution for 24 hr/day, or when tested for schedule-induced-polydipsia 3 hr/day. The results indicate that bypassing a large segment of the jejunum and ileum does not disrupt regulatory drinking in the rat, but it does limit their ability to consume large volumes of fluid.     

Prandial drinking following septal lesions in rats

Septal rats maintained on a 23 hr food deprivation schedule drink more water than operated controls during the daily 1 -hr access to food pellets. Examination of the eating and drinking pattern showed that the elevated septal water intake arose from the adoption of an abnormal prandial drinking pattern similar to that previously reported for recovered lateral hypothalamic rats. The septal rats interrupted their eating once every two pellets on average by short bouts of drinking. It is suggested that the occurrence of prandial drinking resulted from a deficit in the control of salivation following septal damage.     

Altered spontaneous and osmotically induced drinking for fowls with permanent access to dilute quinine

Fowls were given a dilute quinine solution as their sole source of fluid, and effects on normal ingestion and on drinking responses to dipsogenic stimuli were examined. Compared to controls with water, daily fluid intakes were depressed by 25% with quinine. There was no significant effect of quinine on food intake, but growth was suppressed slightly. Drinking in response to hypertonic NaCl injections was attenuated with quinine, and whereas an initial peak in water intake was seen directly after hypertonic NaCl injection, this was absent with quinine. Moreover, increases in quinine intake after hypertonic NaCl injections were insufficient to restore normal osmolality. Plasma analyses indicated that birds drinking quinine were permanently dehydrated and, unlike birds with water, they appeared to reduce the hyperosmolality induced by hypertonic NaCl injections in the absence of drinking. In contrast, drinking responses to angiotensin were generally similar with quinine and water, although birds drinking quinine tended to stop sooner with the highest dose of angiotensin. These results support previous suggestions that osmotic thirst is of primary importance in control of normal drinking, but also demonstrate that birds tolerate a degree of dehydration if a suitable fluid source is unavailable.     

Zona incerta lesions: regulatory drinking deficits to intravenous NaCl, angiotensin, but not to salt in the food

Rats with bilateral damage to the anterior zona incerta (ZI) showed small and delayed drinking responses after IP hypertonic NaCl injection, but they normally excreted most of the salt load within 6 hr. The impaired drinking responses were also evident after nonpainful intravenous (IV) NaCl infusions. After nephrectomy, rats with complete ZI lesions did not drink within 24 hr of the NaCl infusion. Rats with less complete lesions showed reduced and delayed drinking. In contrast to these profound osmoregulatory drinking impairments, all of the lesioned rats increased their water to food ratio when fed a 3% NaCl-supplemented diet. ZI lesioned rats did not drink in response to IV infusions of angiotensin II. The role of the ZI in drinking behavior is discussed in terms of the paradigm-dependent nature of these results, and parallels with other findings are considered.     

Differential effects of estradiol on drinking by ovariectomized rats in response to hypertonic NaCl or isoproterenol: Implications for hyper- vs. hypo-osmotic stimuli for water intake

We examined the effects of estradiol on behavioral responses to osmotic challenges in ovariectomized (OVX) rats to test the hypothesis that estradiol enhances sensitivity to gradual changes in plasma osmolality (pOsm) in stimulating water intake. Despite comparably elevated pOsm after a slow infusion of 2 M NaCl, the latency to begin water intake was significantly less in estradiol-treated OVX rats compared to that in oil vehicle-treated rats. Other groups of OVX rats were injected with isoproterenol, which increases circulating angiotensin II. These rats then were given 0.15 M NaCl to drink instead of water, to prevent decreased pOsm associated with water ingestion. Isoproterenol stimulated 0.15 M NaCl intake by both groups; however, estradiol-treated rats consumed less 0.15 M NaCl than did oil-treated rats, findings that are similar to those reported when estradiol-treated rats consumed water. The estradiol enhancement of sensitivity to increased, but not to decreased, pOsm suggests that estradiol has directionally-specific effects on osmoregulatory drinking. Moreover, the estradiol attenuation of 0.15 M NaCl intake after isoproterenol suggests that estradiol effects on osmoregulatory drinking are independent of those on volume regulatory drinking.     

Vigorous intake of oil emulsion caused by chronic food deprivation remains after recovery in rats

Oil emulsion intake over a 30-min period was compared under different dietary conditions (ad libitum feeding and chronic food deprivation) and at various concentrations of oil in rats. The pattern of intake for each dietary condition was extremely different. Food-deprived rats ingested more emulsion when the solution was thicker but intake amount became less at too high a concentration. Ad libitum feeding rats ingested less emulsion than deprived rats with no difference among the concentrations. Rats on a restricted diet clearly differentiated between concentrations, selecting the thicker emulsion when provided two-bottle selection between 10% oil and some other concentration. On the other hand, rats fed ad libitum differentiated between only extremely weak solutions. The vigorous intake of oil emulsion induced by chronic food deprivation was maintained after 2 weeks of normal feeding. Significant difference between prior dietary conditions was maintained at lower concentrations. Dietary timing for food-deprived rats affected little on emulsion intake. These results indicate that response to oil emulsion intake differs by concentration in rats.     

Gastric emptying and intestinal absorption of ingested water and saline by hypovolemic rats

Recent experiments showed that in a one-bottle test conducted 16 h after sc injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water or 0.30 M NaCl in an initial drinking episode but did not empty the ingested fluid from the stomach or absorb it from the small intestine very rapidly, certainly not as rapidly as when 0.15 M NaCl was consumed (Smith et al., Am J Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of water and 0.30 M NaCl ingestion and the movement of consumed fluid through the gastrointestinal tract when PEG-treated rats were given a two-bottle delayed-access test. We found that both fluids always were consumed in the first drinking episode, that the fluid mixture ingested was equivalent to 0.10-0.15 M NaCl, and that gastric emptying rate and net fluid absorption from the small intestine usually were much faster than when PEG-treated rats drank either water or hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic rats in the same episode adaptively facilitated the movement into the circulation of a near-isotonic fluid that is ideal for restoring plasma volume deficits.