Forty mouse strain survey of water and sodium intake

We measured voluntary water and sodium intakes of 40 inbred strains of mice. Groups of approximately 10 males and approximately 10 females from each strain received a series of 48-h tests with a choice between a bottle of water and a bottle of one of the following: water, 25, 75, and 225 mM NaCl, 25, 75, and 225 sodium lactate. Sodium solution intakes were influenced by strain, sex, anion and concentration: Nine strains drank significantly more chloride than lactate, and only one strain (I/LnJ) drank significantly more lactate than chloride. The other 30 strains drank similar volumes of chloride and lactate. Sodium intakes were higher in females than males of 8 strains and did not differ by sex in the other 32 strains. Some strains had consistently high sodium intakes and preferred all sodium solutions to water (129S1/SvImJ, MA/MyJ, NZW/LacJ and SWR/J), some showed indifference (i.e. preferences not significantly different from 50%) to all concentrations tested (A/J, C57BL/6J, FVB/NJ and SEA/GnJ), and some had consistently low sodium intakes (AKR/J, C3H/HeJ, C57BL/10J, CBA/J, DBA/2J, I/LnJ, JF1/Ms, LP/J, NON/LtJ, PERA/EiJ, PL/J, and RIIIS/J). The results illustrate the diversity of voluntary sodium intake in mice and will assist in the selection of appropriate strains for focused genetic and physiological analyses.     

Increased intake of water and NaCl solutions in omega-3 fatty acid deficient monkeys

We previously reported that long-term omega-3 fatty acid deficiency is associated with increased water intake in rhesus monkeys. To determine whether the increase was specific to water, intakes of salt solutions were measured in 15-minute single-bottle tests. Deficient monkeys drank at least twice as much of all NaCl concentrations as controls. Overall intake decreased as salt concentration increased. In 2-bottle preference tests, deficient monkeys again drank more total fluid but neither preferred nor avoided normal saline compared to controls. When deprived of water, deficient monkeys concentrated urine as well as controls, demonstrating that the increased intake was not a result of renal failure or diabetes insipidus. Omega-3 fatty acids have roles both in neural membrane function and in metabolism of prostaglandins and other eicosanoids. Omega-3 fatty acid deficiency may affect drinking through changes in one or both of these functions.     

Consumption of solutions containing sodium chloride is enhanced in female oxytocin-deficient mice

Intact and ovariectomized oxytocin (OT)-deficient (OT-/-) and wild-type (OT+/+) mice were tested for consumption of 0.5 M NaCl solution or tap water in a 2-bottle choice test. During 3 days of acclimation, voluntary ingestion of NaCl was equal between genotypes. After overnight fluid deprivation, intact OT-/- mice ingested 2 times more NaCl solution than OT+/+ mice in the 6th hr, but not the 1st hr, after reintroduction of fluid. Ovariectomized mice consumed less than intact mice after overnight fluid deprivation. When a 0.2 M NaCl solution was administered for 6 days in ovariectomized mice, OT-/- mice voluntarily consumed greater amounts than OT+/+ mice. After overnight fluid deprivation, consumption by OT-/- mice was 3 times that of OT+/+ mice at 1 hr and 2-fold greater after 6 hr. Enhanced intake of NaCl-containing solutions in female OT-/- mice suggests that central OT may be an important inhibitor of sodium consumption.     

The spontaneously hypertensive rat's preference for salted foods

Sprague-Dawley rats drink mild salt (NaCl) solutions in preference to plain water. In contrast, rats of this strain are less likely to show preferences when salt is tested in food. Others have established that rats of the spontaneously hypertensive strain (SHR) have greater preferences for salt water than do their normotensive counterparts (WKY). The question addressed in the present research was whether SHR rats would show an enhanced salted food preference when compared with WKY rats. SHR and WKY rats were given choices between a variety of salted and unsalted foods. When tested with potato chips, no major strain differences in salt preferences were observed; depending on concentrations, rats ate either equal amounts of salted and unsalted chips or avoided salted chips. However, when tested with liquid milk products (heavy cream and half & half), SHR rats showed both higher salt preferences and consumed more salt. The SHR actually preferred these products salted, whereas the WKY rats, like Sprague-Dawley rats, never ate more salted milk than plain milk. When tested with skim milk, SHR and WKY did not differ; both preferred the milk salted. In order to test the effect of physical state (or texture) upon salt preference, the skim milk was gelled. Salt preferences of the SHR rats fell to 50% whereas the salt preferences of the WKY rats remained unchanged.     

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.     

The influence of previous salt ingestion on the renal function of sheep subjected to intravenous hypertonic saline

1. Sheep, which had access to a solution containing 1.3% sodium chloride as their sole source of drinking water for 6 months or more, were infused with a hypertonic solution (10%) of sodium chloride, and their ability to tolerate this salt load was compared with that of a similar group of sheep which drank only rain water.2. The sheep which drank the rain water were often affected by the infusion and exhibited signs resembling potassium deficit. No such signs were apparent in the animals which consumed saline water.3. Glomerular filtration rates were increased in all sheep by the hypertonic saline infusion, the increases being greater in the sheep which were maintained on the saline water. Effective renal plasma flow rates, though extremely variable, behaved in a similar manner.4. Plasma values for sodium and chloride were increased in all sheep, but remained at a higher level for a longer period in the sheep which consumed rain water. The diuresis produced by hypertonic saline appeared to persist for a longer period in the sheep which drank rain water, while the excretion of sodium and chloride tended to be greater in the sheep maintained on saline water.5. Plasma potassium was reduced in all sheep and urinary excretion of potassium increased. The latter response was more pronounced in the sheep which drank the rain water.6. Filtered loads of sodium, chloride and potassium were greater in the sheep which were accustomed to drinking saline water. However, the amounts of potassium excreted were greater than those filtered in the rain water sheep and less than those filtered in the sheep which drank saline water. It therefore seems that secretion of potassium into the kidney tubules predominated in the former group and reabsorption prevailed in the latter.7. Reabsorption of free water in excess of solute was greater in the kidney tubules of the sheep which drank saline water.8. Increased blood volume and greater dilution of plasma proteins occurred in the sheep which drank rain water.     

Mouse strain differences in operant self-administration of ethanol

By the use of operant conditioning procedures, we determined whether mice from two strains, C57BL/6J and BALB/cJ, differ in ethanol-reinforced behavior. To establish ethanol as a reinforcer, drinking was induced by feeding mice prior to the 30-min experimental session. Initially mice received water and then a series of increasing ethanol concentrations (1, 2, 4, and 8%, w/v) in response to a lever press. The volume of liquid consumed per unit of body weight remained relatively constant across concentrations, and thus the amount of ethanol consumed (g/kg) increased with increases in ethanol concentration. At all concentrations the C57BL/6J mice drank larger volumes than the BALB/cJ mice. After shifting the time of feeding from before to after the session, the consumption of 8% ethanol declined 56% for the C57B/6J mice and 81% for the BALB/cJ mice. To determine if ethanol was serving as a reinforcer, behavior and intake were then compared during ethanol and water availability. The ethanol consumption of the C57BL/6J mice markedly exceeded the water consumption and resulted in blood ethanol levels of 199 ±27 mg/dl. These levels significantly exceeded the 8% ethanol intake of the BALB/cJ mice, while 0% intake was low and not significantly different between strains. The 8% ethanol drinking of the BALB/cJ mice did not differ from their water drinking. Thus, ethanol was established as a positive reinforcer for C57BL/6J mice but not for BALB/cJ mice.This research was supported in part by New Investigator Research Awards AA-06104 and AA-06924 to Frank R. George from the National Institute on Alcohol Abuse and Alcoholism and by Research Scientist Development Award DA-00007 to Richard A. Meisch from the National Institute on Drug Abuse.     

Selective Breeding for High and Low Alcohol Preference in Mice

High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, out-bred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.     

Voluntary lactose ingestion in gerbils, rats, mice, and golden hamsters.

Over a period of 20 days, adult male gerbils, rats, mice, and hamsters were allowed to choose between tap water and a sugar solution (either sucrose, glucose, or lactose) presented in increasing concentrations (maximum concentration = 24% weight/volume). Rats, mice, and hamsters preferred both glucose and sucrose solutions to water across a wide range of concentrations; gerbils preferred sucrose solutions at concentrations of 8% and above, but preferences for glucose solutions were not significant. Gerbils, mice, and rats did not prefer lactose solutions to water at any concentration, and actually preferred water at higher lactose concentrations; in contrast, hamsters preferred lactose solutions to water at concentrations of 4% and above, and never preferred water to lactose solutions. As solution concentrations increased, all species consumed increasing amounts of glucose and sucrose (i.e., solute). The lactose intake of gerbils, rats, and mice tended to remain quite low even as solution concentration increased; in contrast, the lactose intake of hamsters was substantially greater than that of other species and increased to a maximum of 1.95 g/100 g body weight/day at the 24% concentration. These results indicate that gerbils and mice, like rats, have a low preference for lactose and consume very little of this disaccharide, and confirm that golden hamsters are exceptional in demonstrating both a preference for lactose solutions and an apparent tolerance to the effects of ingestion of substantial amounts of lactose.     

Salt preference in rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

Brattleboro rats are homozygous for diabetes insipidus (HO-DI), lacking the ability to synthesize vasopressin. Besides increasing water consumption, HO-DI rats may compensate for their excessive renal water loss by reducing their intake of and preference for substances that elevate plasma osmolarity. In two experiments we assessed this possibility. In Experiment 1, salt preference of HO-DI and control Long-Evans (LE) rats was measured by presenting the rats with two tubes: one filled with water and the other with NaCl. In the first part of the experiment, 18 NaCl concentrations were presented in increasing order (from 6 to 300 mM). In the second part, other groups of HO-DI and LE rats were presented with 6 concentrations of NaCl, ranging from 6 to 450 mM in either increasing or decreasing order of concentrations. In Experiment 2, preference for 6 concentrations of citric acid ranging from 0.1 to 6 mM was assessed. With NaCl concentrations greater than 100 mM, intake and preference declined rapidly for the HO-DI group but very gradually for the LE group. In contrast, the HO-DI rats preferred all citric acid solutions more than LE rats. The results suggest that HO-DI rats compensate for their inability to concentrate urine not only by increasing water consumption, but also by decreasing consumption of and preference for salty solutions.     

Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.

Central amygdaloid nucleus lesions in rats had no effect on recovery of preoperative body weight and food consumption levels. The brain damaged rats also recovered preoperative levels of water consumption as rapidly as control rats but then developed a mild but persistent hypodipsia. The experimental rats also drank less than control rats when food deprived and showed marginally reliable decreases in 0.1% quinine solution consumption and latency to consume a novel food. There was no detectable lesion effect on 0.1% saccharin solution consumption, exploration of a novel environment or formation of a learned taste aversion. It is suggested that the central amygdaloid nucleus has a role in mediating the relationship between food and water intake and in some taste mediated consummatory behavior.     

Sucrose intake and fasting glucose levels in 5-HT(1A) and 5-HT(1B) receptor mutant mice

Serotonin (5-HT)(1A) and 5-HT(1B) receptors have been implicated in the incidence and treatment of depression in part through the examination of animals lacking these receptors. Although these receptors have been repeatedly implicated in ingestive behavior there is little information about how 5-HT(1A) and 5-HT(1B) receptor mutant mice react to solutions of varying palatability. In the present experiment male and female 5-HT(1A) and 5-HT(1B) mutant and wild-type mice were presented with increasing concentrations of sucrose using a two-bottle choice procedure. In addition fasting blood glucose levels were assessed. Both male and female 5-HT(1B) mutant mice drank more sucrose than WT mice but also consumed more water. Female, but not male, 5-HT(1A) mutant mice similarly showed increased sucrose consumption, but did not demonstrate increased consumption of water. In addition, the pattern of increased sucrose consumption over genotype and sex was related to fasting blood glucose concentrations such that levels in male 5-HT(1B) mutant mice were reduced relative to wild-type and 5-HT(1A) mutant males, but similar to those of females. The findings in 5-HT(1B) mutant mice emphasize the role of the 5-HT(1B) receptor in regulating ingestive behavior, whereas female sex hormones and 5-HT(1A) receptors may interact to alter sucrose consumption in 5-HT(1A) mutant mice. In addition, these findings may have implications for the role of these receptors in the incidence and treatment of depression since the intake of sucrose has been used as an index of anhedonia in animal models of depression and antidepressant efficacy.     

Sex differences in the taste preference for a salt solution in the rat

A two-bottle free choice method was employed to investigate the water and 3% NaCl solution intake in rats of both sexes from the age of 30 days to adulthood. No sex difference was observed until the period of sexual maturation was reached. From that time on females drank more of the salt solution than males; the sex difference was apparent also in the NaCl concentration in total fluids consumed. These sexual differences existed also in adult rats which had been gonadectomised at the age of 10 days. After the free choice experiment was completed, the total RNA content in cells of hypothalamus and hippocampus of adult males and diestrous females was investigated. In females no effect of increased salt intake was seen. In males increased salt intake was associated with increased RNA content in all cells investigated. The role of the hypothalamus in sexual differentiation of salt intake is discussed.     

Exogenous adrenocorticotrophic hormone does not elicit a salt appetite in growing pigs

In rodents, rabbits, and sheep, exogenous adrenocorticotrophic hormone (ACTH) leads to a marked increase in sodium appetite. It has been suggested that if pigs show a similar response to stress, an appetite for salt could increase their attraction to blood and contribute to the development of tail biting. The aim of this study was to examine the effects of ACTH on salt appetite in growing pigs. Individually housed Yorkshire pigs (45 kg) were divided into three groups of four. Group 1 had free access to water, 0.5 M NaCl, and 0.5 M KCl solutions; Group 2 to water, 0.5, and 0.25 M NaCl solutions; Group 3 to water, 0.25, and 0.125 M NaCl solutions. Intramuscular injection of long-acting synthetic ACTH (50 IU twice daily for 5 days) did not elicit increases in intakes of any of the available salt solutions compared to pretreatment intakes. However, there was a 1.6-fold increase in both water and feed intake during ACTH treatment. ACTH treatment also stimulated significant increases in salivary cortisol concentrations. Although increases in salivary cortisol concentrations and in water and feed intake indicate that there were physiological responses to the treatment, exogenous ACTH given for 5 days did not elicit a sodium appetite in growing pigs. These findings do not support the notion that a stress-induced salt appetite serves as an underlying mechanism for tail biting.     

Neonatal ablations of the gustatory neocortex in the rat: taste aversion learning and taste reactivity

Rats sustaining ablations of gustatory neocortex (GN) at 2, 10, 20, or 60 days of age were compared with control rats in the acquisition and extinction of a learned taste aversion; in addition, these rats were tested for taste preference across five concentrations of sodium chloride solution. Results indicated that GN ablation disrupted aversion acquisition and extinction regardless of age at surgery. Taste response functions for the sodium chloride solutions shown by all GN groups of rats mirrored those of control rats: preference (relative to water baseline) for middle concentrations and rejection of the strongest salt concentration. There was a suggestion that the 20- and 60-day-old GN rats were hyperresponsive to the suprathreshold concentrations of NaCl (except the strongest concentration). The increased response to salt solutions in the 20- and 60-day GN rats may have been related to the significant decreases in water consumption relative to that of normal rats. Water consumption of control rats and GN rats in the 2-day and 10-day groups was essentially equal. It is concluded that infant ablation of the GN does not spare normal taste aversion learning and that rats with GN ablations, regardless of age at surgery, respond in a normal manner to the hedonic aspects of sodium chloride solutions.     

Parametric study of the regulatory capabilities of rats with rostromedial zona incerta lesions: Responsiveness to hypertonic saline and polyethylene glycol

Rats with lesions in the dorsomedial zona incerta (ZI): (1) were hypodipsic; (2) drank little or nothing during periods of food deprivation; (3) drank little or nothing after injections of 5 ml of 0.50 M, 0.75 M, 1.0 M or 2.0 M NaCl solutions (some animals displayed delayed responses to the highest dose, 6 and 24 hr after the injection); (4) drank normal quantities of water or saline after 5 ml of 15%, 20%, or 30% PG (half of the animals that had shown absent or severely impaired responses to hypertonic saline; the other half did not drink saline or water in response to any dose of PG except the highest—5 ml of 30%); (5) sharply reduced or abolished sodium appetite; (6) reduced or abolished the feeding response to 2-DG without affecting ad lib food intake. Similar effects on 2-DG eating and sodium appetite (but not on water intake under ad lib or food-deprivation conditions, or on drinking in response to hypertonic saline or PG) were produced by lesions in ventral thalamus or dorsomedial hypothalamus.     

Body weight reducing effect of oral boric acid intake

Background: Boric acid is widely used in biology, but its body weight reducing effect is not researched.Methods: Twenty mice were divided into two equal groups. Control group mice drank standard tap water, but study group mice drank 0.28mg/250ml boric acid added tap water over five days. Total body weight changes, major organ histopathology, blood biochemistry, urine and feces analyses were compared.Results: Study group mice lost body weight mean 28.1% but in control group no weight loss and also weight gained mean 0.09% (p<0.001). Total drinking water and urine outputs were not statistically different. Cholesterol, LDL, AST, ALT, LDH, amylase and urobilinogen levels were statistically significantly high in the study group. Other variables were not statistically different. No histopathologic differences were detected in evaluations of all resected major organs.Conclusion: Low dose oral boric acid intake cause serious body weight reduction. Blood and urine analyses support high glucose, lipid and middle protein catabolisms, but the mechanism is unclear.     

Blood volume changes and arginine vasotocin (AVT) blood concentration in conscious fresh water and salt water adapted ducks

Blood volume changes consisting in the removal and reinfusion respectively, of 10% of the estimated blood volume (23.2 ml on average) were induced to determine their effects on the blood concentration of arginine vasotocin (AVT), the antidiuretic hormone (ADH) of birds, in fresh water adapted ducks (water ducks) with blood osmolalities and ADH concentrations similar to those of normally hydrated mammals, and in salt water adapted ducks (salt ducks) with chronically elevated blood osmolalities and ADH concentrations. The investigations were carried out in steady state conditions, when infusion of 1 ml·min^–1 of isotonic saline was matched by the excretion in water ducks and when infusion of 0.4 ml·min^–1 of 1,000 mosmolal saline was matched by the salt gland excretion in the salt ducks.After blood removal, AVT blood concentration (mean ±SE) increased from 6.5±0.4 to 8.4±0.6 pg·ml^–1 in water ducks and from 18.1±1.6 to 22.6±1.9 pg·ml^–1 in salt ducks. The respective blood osmolalities of 297.4±1.4 and 318.6±3.3 mOsm·kg^–1 did not change. Reinfusion of the blood after steady-state conditions had been reattained decreased blood AVT from 7.9±0.7 to 6.7±0.5 pg·ml^–1 in water ducks. In the salt ducks AVT concentration had already returned to the control level before blood reinfusion which induced no further reduction. The blood osmolalities remained unchanged in both groups.During blood removal and reinfusion, the excretion rate of the kidneys in water ducks and the salt glands in salt ducks were temporarily reduced and enhanced respectively, the effect being not symmetrical for salt gland secretion.For water ducks, the volume sensitivity of AVT release was found comparable to that of mammals, when related to the induced blood volume changes, the responses to blood removal and reinfusion being approximately equal in absolute terms. In the salt ducks, the volume sensitivity of AVT release was clearly expressed during blood removal but insignificant during blood reinfusion.Supported by the Alexander v. Humboldt-StiftungSupported by the Deutsche Forschungsgemeinschaft     

Intake of ethanol,sodium chloride,sucrose, citric acid,and quinine hydrochloride solutions by mice: A genetic analysis

Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F₁ and F₂ hybrids were offered solutions of ethanol, sucrose, citric acid, quinine hydrochloride, and NaCl in two-bottle choice tests. Consistent with earlier work, the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride solution and less NaCl solution than did 129 mice. Analyses of each generation's means and distributions showed that intakes of ethanol, quinine, sucrose, and NaCl were influenced by a few genes. The mode of inheritance was additive in the case of ethanol and quinine, for sucrose the genotype of the 129 strain was recessive, and for NaCl it was dominant. Citric acid intake appeared to be influenced by many genes with small effects, with the 129 genotype dominant. Correlations of sucrose consumption with ethanol and citric acid consumption were found among mice of the F₂ generation, and the genetically determined component of these correlations was stronger than the component related to environmental factors. The genetically determined correlation between sucrose and ethanol intakes is consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component.     

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.