J mouse

Physiology and Behavior, Vol. 13, pp. 71-79. Brain Research Publications Inc., 1974. Printed in the U.S.A.

Age-Dependent Polydipsia in the SWR/J Mouse CHARLES L. KUTSCHER AND DEAN G. MILLER

Department o f Psychology, Syracuse University, Syracuse, New York 13210

(Received 14 December 1973)

KUTSCHER, C. L. AND D. G. MILLER. Age.dependent polydipsia in the SP/R/J mouse. PHYSIOL. BEHAV. 13(1) 71-79, 1974. - 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 polydil~ic 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 polydipsla. In females, the increase in water intakes was accompanied by a decrease in intakes of isotonic and hypertoni¢ NaCI 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. ADH

Aging

Diabetes insipidus

Drinking

Kidney

NaCI intake

Polydipsla

IN A STUDY of longevity of inbred mouse strains, Storer [ 19 ] reported that in the SWR/J strain there are two peaks of deaths. The second is apparently related to aging and senescent changes, but the first is related to the development of severe polydipsia and polyuria. Kutscher and Miller (unpublished study) have shown that this polydipsia and concomitant polyuria in the SWR/J mouse is not caused by any defect in the production, storage, or release of vasopressin (ADH). Instead, polydipsic SWR mice have more ADH in the posterior pituitary and urine than nonpolydipsic white Swiss mice, but the kidneys are refractory to it. Furthermore, some of the polydipsic mice developed large lesions in the medullary portion of the kidney, a condition which should result in reduced ability to concentrate urine. The present paper provides a description of the development of polydipsia with age in the SWR/J mouse and the changes in drinking of water relative to various solutions. Most of these changes are compatible with the notion that there is an age-related degeneration of the kidney with concomitant development of renal concentrating deficits, i.e., nephrogenic diabetes insipidus (NDI).

experiments when deiordzed water was used. All mice were experimentally naive at the beginning of the experimental series. Some animals were tested in several subsequent experiments. Apparatus. In the breeding and holding room and in the test rooms, lights were on for 12 hr/day: Temperature was maintained at 21 + loC and humidity at 60 ± 10%. At the beginning of testing 142 of the mice were removed from group housing and placed in individual steel cages 0 2 . 5 × 18 × 15 cm) with hardware cloth floors and ceilings. The remaining 32 were used only in Experiments 1 and 4 and were tested in larger cages (25 × 18 × 15 cm). Solutions were given in 50 or 100 ml eudiometer tubes graduated in 0.2 ml units and fitted with steel drinking spouts. All solutions used in tests were mixed in deionized water. Procedure. Daily water intake was the first measure taken on all animals. Seven groups of mice r a n ~ n g in age from 4 - 2 0 mo were tested (see Fig. l for ages and N of each group). After two weeks of adaptation to the test cages, water intakes and body weights were recorded for five consecutive days with food avilable ad lib.

EXPERIMENT 1

Figure l shows mean five-day water intakes plotted as a function of body weight (relative water intakes). By this measure water intakes of the females were consistently higher than for the males at every age interval tested. For both sexes water intakes increased sharply with age within the 9 - 1 2 mo interval. It may be seen that mean water intakes of females 12 mo and older exceeded body weights. Relative water intakes are also shown for female mice obtained from a cross between SWR/J and C57BL/6J mice and for male and female mice of the C57BL/6J and C3H/HeJ strains and the derived F-I and F-2 generations.

Method Animals. The animals in the following series of experiments were 87 males and 87 females of the SWR/J inbred mouse strain, bred in this laboratory from stock received from Jackson Laboratory, Bar Harbor, Maine. Ages at testing ranged from 4 - 2 0 mo. From time of weaning until the beginning of the experiment, animals were housed in plastic cages in groups of 5 - 2 0 . Animals were fed Purina chow pellets and were given tap water to drink except during the 71

Results

72

KUTSCHER AND MILLER $

-r

4

6

11

12

/kge (months)

14

18

II

20

FIG, 1. Mean relative water intakes (rrd/100 g body weight) for SWR/J mice at various ages. For sake of comparison, mean water intakes are also shown for a ezoss between the SWR/J and C57BL/6J strains and for C3H/HeJ, C57BL/6J, and F-I and F-2 generations derived from C3H/HeJ and C57BL/6J strains. Since there were no significant differences in water intakes among these last four strains, the data from the groups were plotted as a single point for each sex. Relative water intakes for all these various strains were well below those of SWR/J mice at a comparable age and well below the youngest SWR/J mice used in this experiment (4 roD). Frequency distributions (not shown) of absolute water intakes (ml) plotted separately for the various age groups showed similar results to those shown in Fig. 1 for relative water intakes. Mean absolute water intake and the variability of these measures increased with age. A sharp increase in water intakes occurred between 8.5 mo and I0.5 mo. For 10.5 mo females, 19 out of 22 mice drank more than the highest water intake of the 8.5 ml group. The other strains tested showed low mean water intakes and low variability. EXPERIMENT

2

In most animals, a considerable portion of the free water intake is utilized in the digestion of food and the correction of osmotic imbalances produced by the postingestional consequences of eating [I I ]. The SWR/J mouse, with kidneys refractory to A D H , probably utilizesa considerable portion of its daily water intake in the ingestion and digestion of food; therefore, food deprivation should sharply reduce water intake. Method Water intakes were measured for 49 male and 40 female

cage-adapted SWR/J mice, age 8 . 5 - 2 0 mo during one day of ad lib feeding, one day of total food deprivation, and one day of refeeding. One-third of the animals were subjected to deprivation on each of three consecutive days so that intakes of nondeprived mice could be monitored to determine whether environmental changes were producing anomalous intakes on any of the test days. Results As shown in Fig. 2, food deprivation reduced absolute water intakes for both males and females in all age groups. On the food,deprivation day, 38 females out of 40 drank less than on the preceding day of ad lib feeding. For the males, 42 out of 49 drank less. On the refeeding day, water intakes increased to virtually the same level as before deprivation. Forty out of 49 males and 40 out of 40 females drank more on the refeeding day than on the fooddeprivation day. Analysis of variance indicated that on the food-deprivation day there were no significant differences in water intakes among age ~'oups for both the females, F(3,36) = 2.65, p>O.05, and the males, F(3,45 = 1.40, p>O.05. Age differences were found for females, F(3,36) = 17.67, p<0.01, and males, F(3,45) = 8.36, p
AGE-DEPENDENT POLYDIPSIA

73

r ' - ' l 8.5 too. I 10.5 me. i 12.5 too. 14-20 no.

gmlos

A.L.

DeF.

Etc.

A.L.

I),p.

Itec.

FIG. 2. Mean water intake for SW~J ~ during one day of ad libitum feeding (AL), one day of total food deprivation (Dep) and ¢me day of refeeding or recovery (Rec). on the postdeprivation day. There were no significant differences among age groups in the relative weight lost (g/I O0 g predeprivation body wt) during the one day o f total food deprivation. There is no indication that the absence of polydipsia during food deprivation resulted in greater dehydration o f the polydipsic older animals over the nonpolydipsic younger animals, assuming that weight loss gives an approximation of the degree o f dehydration. EXPERIMENT 3

The temporal pattern of drinking during a 24-hr period as a function o f age was studied. There are at least two important questions to be considered. First, is there a sharp circadian r h y t h m o f drinking in the SWR/J mouse? Such rhythms have been reported in drinking [8] and in general activity [1] for other strains o f mice. Secondly, is such a r h y t h m altered by the development o f polydipsia? Method

Hourly water intakes for a 24-hr period were recorded for 50 male and 53 female SWR/J mice aged 8 - 2 0 mo. Twenty-four males and 24 females were deprived o f food

during this period but the rest were allowed food ad lib. Mice had been exposed since birth to the 12-hr light cycle used in this experiment. Water intake measurements were made during the dark cycle with the aid of a small flashlight. Measurements were begun I hr after the onset of the dark cycle. Results

Although water intakes were measured hourly, the data were combined into 2-hr segments to facilitate analysis and presentation. In Fig. 3 all age groups are combined in both the ad lib and deprivation conditions to produce the water intake curves shown. Under ad lib conditions a clear circadian r h y t h m is shown for both sexes with the lowest water intake occurring approximately midway into the light cycle and peak drinking occurring in the fLrst half of the dark cycle. The drinking is clearly entrained to a 24-hr cycle, but is not sharply altered by the onset or offset of light. Mean drinking decreased gradually following light onset and increased gradually in the second half of the light period long before onset of the dark cycle. These drinking rhythms are markedly similar to the general activity curves in mice reported in other experiments [1,8].

74

KUTSCHER AND MILLER

5

Mulos

Fomolos A.L.

O~-"O

E

o3

El

B

41hal

A.I.. •J

i C~4

Hours FIG, 3. Mean water intake (mi) for SWR/J mice given food ad lib (AL) or during total food deprivation (Dep) plotted in 2-hr intervals over the test day. The circadian rhythm of drinking is less well-defined in the food-deprived mice, but in general inverted U-shaped functions were observed for both males and females with lowest water intakes occurring in the latter half of the dark period and the first half of the light period. In both sexes, drinking was clearly increasing in the second half of the light cycle, just as was the case for the nondeprived mice, showing that this aspect of the drinking xhythm does not depend upon the presence of food, although food deprivation does decrease the level of absolute water intake. In Fig. 4, circadian rhythms in drinking are plotted as a function of age for nondeprived mice. Since mice differed in absolute (ml) and relative intakes (ml/100 g weight) as a function of age, water intakes for each 2-hr period were converted into a percentage of total daily intake for the test day. It can be seen in Fig. 4 that the circadian rhythms are markedly similar for the various age groups and for both sexes. Thus, the development of polydipsia with age does not alter the basic circadian rhythm of drinking, but causes a proportionate increase in drinking in each of the 2-hr time units similar to the manner in which food deprivation increases drinking in the C3H/HeJ strain [ 101. EXPERIMENT 4

Salt intakes were studied under the forced intake conditons of a singie-tube test in which a salt solution was offered during a test period without water present. The

animal's response is not preference but mere acceptance. If the SWR/J mouse has progressive deterioration of renal concentrating ability with age, then intake of the more concentrated NaCI salt solutions should decline with the decline in renal concentrating ability.

Method Thirty-two male and 30 female mice were used in this experiment, ages 6, 10, 12.5 and 1 5 - 2 2 mo. There were seven or eight mice of each sex in each age group. In order to minimize the expected dehydration stress on polydipsic animals, especially when the higher NaCI concentrations were used, NaC1 test periods were limited to 12 hr with 36 hr of tap water availability given to enable the mice to recover any weight loss. The NaCl solutions used were 0.0, 0.3, 0.7, 1.0, 1.5, and 2.0% NaCI presented according to a modified Latin square design. Mice were weighed at the beginning and end of the test period.

Results Mean 12-hr intakes of the various salt solutions are plotted in Fig. 5 as a function of sex and age. For the females, salt intakes (ml) decreased significantly with increasing concentrations, F(5,28) = 57.98, p<0.01, and varied with age, F(3,28) = 3.55, p<0.05; however, there was a significant

AGE-DEPENDENT POLYDIPSIA

75

Females

12

e,-e li too. ~,,o 12.5 me. 14- 20 too.

o 10 I

am

4m ,_o

,,.4 O

G, 4

6

e

10

Males o]

12 14 Hours

16

111 20

22

24

o.,,,,oe too. eM.412.5 me. o,,,,o 14- 20 m0.

I i

uGm

4in

0 k..-

"g4..

2

4

6

|

10

12 14 Hoers

16

10

20

22

FIG. 4. Water intakes for the 24-hr test period for SWR/J mice receiving food ad lib plotted in 2-hr intervals as a percentage of total intake in order to facilitate comparisons of mice with different levels of water intake. interaction, F(I 5,140) = 4.24, p <0 . 0 1 , due to the fact that the 6 mo age group drank significantly less water than the other groups, but significantly more of the 1.5 and 2.0% solutions. When the data from the 6 mo group were arbitrarily eliminated from the analysis, no significant interaction was

found although significant effects due to NaCl concentration, F(5,21) = 50.64, p<0.01, and age, F(2,21) = 5.81, p< 0.01, persisted. The NaC1 intakes for the males, unlike those of the females, showed no significant age effect. Significant differences were found due to solution concentration, F(6,26) =

76

KUTSCHER AND MILLER

25

37.79, p < 0 . 0 1 , and the interaction was significant, F(I 5,157) = 2.64, p < 0.01. Inspection of the data suggested that the interaction was cuased by the low water intake of the 6 m o group. Analysis of the data w i t h o u t the water intakes showed significant differences due to concentration, F(4,26) = 77.36, p < 0 . 0 1 , but no significant differences in regard to age and no interaction. In view o f the d e v e l o p m e n t of polydipsia in females at a p p r o x i m a t e l y 9 m o as shown in E x p e r i m e n t 1, it is of interest to n o t e that m e a n intakes o f the 6 m o group e x c e e d e d those o f the 10 m o group for b o t h 1.5% (t = 2.29, d.f = 14, p < 0 . 0 5 ) and 2.0% solutions (t = 2.94, d f = 14, p < 0 . 0 2 ) . None o f the male groups had water intakes significantly greater than water intake of the 6 m o female group, a fact which may account for the lack o f an age effect in male NaCI acceptance.

I

[fonelos

\

,-,,o

6 no.

~'--"~" IO n o .

0_15

• .-,o

I1.$ no.

,-,-o

15-11 NO.

I an

I|

1.3

t7

1.0

1.5

EXPE RIMENT 5

2.O

°/to NanCl

25

20

~lS

The a d d i t i o n o f saccharin to water has been f o u n d to increase intakes in rats [ 16 ] and in mice [ 5 ]. Saccharin was used here to see ff ~ could be increased, particularly in the polydil~lic animals where water intakes were already quite high. The a d d i t i o n o f saccharin to water allows the palatability o f the solution to be altered w i t h o u t imposing any signficant osmotic load on the animal.

I malos J .

0.--06 too. * - - * lO me. *~* 12.5 m o.

0~0

"

Method T w e n t y - f o u r male and 24 female mice on which average water intakes had been d e t e r m i n e d were given 0.2% sodium saccharin in place o f water to drink for one day. Five days later the one-day test was repeated with 0.5% saccharin.

15-22 too.

i am,

Results

--'10

Intakes of water and saccharin are s h o w n in Table 1. It may be seen that b o t h 0.2 and 0.5% saccharin concentrations p r o d u c e d intakes" greater than that o f water in all the age groups, even for the older polydipsic females. Within each age group there were no significant differences in intakes b e t w e e n the t w o saccharin solutions. 0

EXPE RIMENT 6

o NaCI

Intake o f h y p o t o n i c and h y p e r t o n i c sucrose solutions were studied for two basic reasons. First, sucrose, like saccharin, is a highly palatable substance which has been

FIG. 5. Mean NaCI intakes (ml) for SWR/J mice during a 12-hr test period in a single-tube test (salt acceptance).

TABLE 1 ABSOLUTE INTAKES OF WATER AND SACCHARIN (ml)

Females

Males

6.5-9 mo

10.5-12.5 mo

6.5-9 mo

10.5-12.5 mo

11

13

11

13

13.0 ± 3.2

25.4 ± 9.0

9.8 ± 1.3

13.2 ± 4.4

0.2% saccharin

*23.4 ± 7.5

*32.8 ± 9.1

"16.4 ± 5.6

"17.0 ± 4.8

0.5% saccharin

"19.6 ± 7.5

*32.4 ± 7.6

"15.7 ± 4.9

"19.7 ± 4.9

N

Pretest mean water intake

*Indicates intakes significantly greater than water intakes (p
AGE-DEPENDENT POLYDIPSIA

77

r - - ! 6 mo. I 10 me. 112.5 too. I 15-20 me.

m

qlD

8 l i

* D

m n

.

Sucrose

s%

SoJutien

FIG. 6. Mean sucrose intake (ml) for SWR/J mice during a 24-hi single-tube test (sucrose acceptance).

found to produce taste-dependent polydipsia in other mouse strains [9] and both solutions should be useful in determining the upper level of fluid intake which can be maintained by the SWR mouse. Secondly, sucrose, unlike saccharin, imposes a transient osmotic load on the animal; however, the sucrose load should be readily metabolized and thus should not require body water for excretion as does NaCI solution and may yield free water during its metabolism. Kakolewski and Deaux [7 ] found in rats with familial D] that aphagia and weight loss developed when rats were given only isotonic NaCI to drink, but not when given isotonic glucose. Method

Sucrose solutions tested were 0, 5, and 20%. A singletube procedure was used as described in Experiment 4 for NaCI except that here test solutions were given for an entire day. Between test days only water was given. Animals were weighed before and after each test session. Animals were 29 male and 28 female mice which had been used previously in the single-tube experiment on NaC1 (Experiment 4). At least a 2-wk recovery period was allowed to eliminate any residual effects of that experiment. Results Intakes of 5 % sucrose were higher than those of water

for all age groups (Fig. 6), indicating that even the most polydipsic mice do not attain the upper limit of drinking potential when given only water. Twenty-seven out of 28 females and 26 out of 29 males showed greater intakes of 5% sucrose than of water. Furthermore, there were no significant differences in 5% sucrose intake among age groups although the age differences were significant for water intakes for both females, F(3,24) = 8.55, p<0.01, and males, F(3,25) = 4.98, p<0.01. There were also no significant age differences when 20% sucrose was given. The 20% sucrose solution depressed intake compared to water in mice older than 6 too. In the three older age groups, 21 out of 21 females and 22 out of 23 males drank less 20% sucrose than water. A series of t-tests done on data of both sexes revealed that there were no significant differences among mean water intakes of the 6 mo group and 20% sucrose intakes of the three older age groups. Thus, the 5% sucrose solution increased intakes and the 20% solution reduced intakes, but in both cases the age differences were obliterated. Body weight data were analyzed to see if the depression of drinking caused by 20% sucrose produced any weight loss in the polydipsic animals as did depression of drinking caused by the NaCI solutions in Experiment 5. No significant weight losses were seen in comparing weights at the end of the 20% sucrose test day to the average weights for the five days prior to the test or to the weights on the

78

KUTSCHER AND MILLER

alternate days in the test sequence when only water was given. Thus, 20% sucrose abolished polydipsia without producing weight loss. Sucrose solutions do provide metabolic water, of course, but calculation showed that only approximately 0.1 ml of water would be formed from the sucrose in 1.0 ml of 20% sucrose, thus indicating that metabolic water could not account for the disappearance of the polydipsia. The ingestion of the 20% solution does reduce the food intake (Kutscher, unpublished observations), thus reducing the water need of the mice. EXPERIMENT 7 This experiment was run to see if a decrease in sucrose preference could be demonstrated with the development of polydipsia, despite the transience of the osmotic load imposed by the ingestion of hypertonic sucrose. Kutscher [9] tested C3H/HeJ, C57BL/6J, and derived generations of mice in a two-tube, two-day test with water paired with 40% sucrose. The water was uniformly rejected and the 40% sucrose was consumed in approximately the same volume as water on a test day when only water was offered.

TABLE 2 WATER AND SUCROSE INTAKE IN POLYDIPSIC AND NONPOLYDIPSIC MICE

Polydipsic

Nonpolydipsie

8

8

N

Significance

Pretest water intake (ml)

20.8

Sucrose intake: % total fluid intake

50.2 ± 13.8

69.1 ± 16.5

t = 2.47 p<0.05

8.6 ± 1.6

6.2 ± 1.6

t = 3.00 p<0.01

91.0 ± 17.6

158.1 ± 35.2

t = 4.83 p<0.01

ml Total fluid intake as % of pretest water intake

5.9

Method

Sixteen male and 16 female mice were used in this experiment. They were well adapted to the calles, having been used in Experiments 1 and 4. Mice were given one test day with two tubes on the cage, one containing water and the other 40% sucrose. Results

Sucrose preference data were statistically analyzed for the eight mice with the highest pretest water intakes (polydipsic) compared to the eight mice with the lowest pretest water intakes (nonpolydipsic). Table 2 shows sucrose preference for the two groups expressed in the conventional manner, i.e., sucrose intake as a percentage of total fluid intake. It may be seen that nonpolydipsic animals exhibited more preference for 40% sucrose than did polydipsic animals; however, the polydipsic mice consumed more mi of sucrose solution. Thus, sucrose preference for the 40% solution, as defined by the preference ratio, declined with the development of the polydipsla despite the transient nature of the osmotic load of the solution. As may be seen in Table 2, nonpolydipsic mice showed an increase in total fluid intake on the test day, but polydipsic mice did not. DISCUSSION There are several important similarities and differences between this study and other published studies of polydipsia and polyuria in mice. In the STR/N mouse strain | 14,15], polydipsia also developed with age and became pronounced at 9 mo of age; however, it developed to the same extent in both males and females. Breeding experiments indicated that STR/N polydipsia was inherited as a recessive trait. Males, but not females, developed a plug in the urethra, distended bladders and hydronephrosis which, in advanced cases, reduced the kidney to a thin-walled sac. As has been shown, polydipsia in the SWR/J mouse was apparently inherited as a recessive trait and was more exaggerated in females than in males, at least up to 22 mo of life. Although studies of renal pathology in the authors' laboratory are currently incomplete, hydronephrosis has

been noted in SWR/J males, but not in females. In several males the bladder distention was so advanced that the mice appeared to casual observation to be grossly obese. As much as 10 ml of urine was recovered from the bladder during autopsy. One important difference between the STR/N mice and the SWR mice is .that the polydipsia was primary in the former and, though the cause of the polydipsia was not determined, the large water intakes were not essential for survival. In the SWR/J mice, the gross water intakes presumably resulted from water losses caused by deficient renal function (Kutscher & Miller, unpublished observations). There were also similarities between the SWR/J mice and the strains studied by Falconer e t al. [4] carrying the Os gene and the DI gene (or genes). Each gene produces a mild defect in renal concentrating ability. When both are present they produce a severe defect with age-dependent polydipsia and polyuria. In general, female mice drank more than males and the polydipsia appeared to be secondary to a polyuria caused by a defect in renal concentrating ability. All of these findings are similar to those in the SWR/J mouse. Basic differences are that in the SWR/J mice polydipsia is not linked to oligosyndactyly and seems not to depend upon a dominant gene. Age-dependent functional and anatomical changes in the kidneys of the SWR/J mice will be covered in a later report, but it seems clear at this point that SWR/J mice and Os and DI mice [4] differ greatly in this regard. Highly polydipsic SWR/J mice have enlarged kidneys and renal lesions which, in the extreme case, obliterated most of the medulla. No such lesions have been reported in the DI and Os animals [ 12,17 ]. Instead, Os polydipsic mice had abnormally small kidneys which were deficient in number of renal glomeruli. The age-dependent changes in drinking reported here are consistent with the notion that progressive renal degeneration occurs with age in the SWR/J mouse strain. The increase in water intakes may accompany a developing refractoriness of the tubules to ADH caused by progressive degeneration of the renal medulla. It is of interest to note that the age differences in drinking were obliterated during total food deprivation (Fig. 2) and when 20% sucrose was

AGE-DEPENDENT POLYDIPSIA

79

offered instead of water (Fig. 6). The former outcome suggests that the age differences in drinking may depend upon an age differential in the amount of water required to ingest and digest food and excrete waste products. Metabolism of Purina Chow should provide a considerable amount of nitrogenous waste products since its protein content is 23%. Fasting also reduced intake of rats with surgically-induced DI [20] and with familial DI [6]. Additional evidence on this point is provided by the fact that offering 20% sucrose instead of water reduced fluid intakes in mice older than 6 mo and abolished age differences in drinking. Since no weight losses were incurred during sucrose drinking, it cannot be argued that the polydipsic mice refused to drink the 20% sucrose because of its hypertonicity. Even 40% sucrose was consumed in the same quantity as water in a two-tube test (Table 2). Feeding of dry sucrose largely abolished polydipsia in rats with familial DI [6], presumably because the sucrose imposed only a transitory osmotic load and produced no metabolic waste products which would require body water to excrete. The decline in NaCI acceptance with the development of polydipsia is also consonant with the notion of progressive deterioration of renal function with age and agrees with studies of DI in rats. In a two-tube test, rats with surgicallyinduced DI drank much more water, but less 1.0% NaC1, than control rats which showed a strong preference for NaCI over water [ 13 ]. The strong preference of the DI rats for water over NaC1 persisted even following adrenalectomy. On the other hand, in a singie-tube NaCI acceptance test, rats with surgically-induced DI [21] or familial DI [7] drank more isotonic saline than water. This apparent difference between the polydipsic SWR/J mouse and DI rat may be due to a greater renal concentrating deficit in the SWR/J mouse or may be due to strain and

species differences in NaC1 acceptance [9,21 ]. It is proposed here that the ingestion of isotonic or hypertonic NaCI solutions in the SWR/J mouse, especially with advanced NDI, may provide little or no free water and may even dehydrate the animal if ingested in large amounts. The precise physiological mechanism underlying the NaCI rejection in the polydipsic females can only be a matter of speculation at this point, but it is possible that osmolality of body fluids may play some role [7]. Stellar, Hyman, and Samet [17] found that hypertonic stomach loads of NaC1 in normal rats produced an increase in the intake of h y p o tonic NaCI solutions and a decrease in intake of hypertonic solutions. Human patients with DI caused by a deficiency of endogenous vasopressin have higher serum osmolality than normal even when water is freely available [3 ]. The failure to find an age effect on salt acceptance in the male mice may be attributed to the fact that polydipsia was not as well developed in males. Mean absolute water intakes (ml) of the three older age groups of the males were not significantly greater than mean intakes of the 6 mo female group (Fig. 5). These data fit well with the notion that both decreased NaCI acceptance and increased water intake reflect progressive deterioration of renal concentrating ability with age. It is possible that the SWR/J strain might serve as a model system for the study of some aspects of aging, especially since degeneration of renal function appears in the aging human [2] and mouse [19]. Possibly the renal degeneration occurring in the SWR/J mouse may be an exaggeration of such processes occurring in other animals. It is also of interest to note that the SWR/J mouse is known to be hypertensive [19]. It is tempting to speculate that hypertension may play some role in the observed renal deterioration.

REFERENCES 1. Aschoff, J. and K. Honma. Att-und individual-muster der Tagesperiodic, Z. vergl Physiol. 42: 383-392, 1959. 2. Davies, D. F. and N. W. Shock. Age changes in giomeruiar f'titration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J. din. Invest. 29: 496-507, 1950. 3. DeWardener, H. E. Polyuria. J. chron. Dis. 11: 199-212, 1960. 4. Falconer, D. S., M. Latsyzewski and J. H. Iseacson. Diabetes insipidus associated with oligosyndactyly in the mouse. Genet. Re~ 5: 473-488, 1964. 5. Fuller, J. L. and C. W. Cooper. Saccharin reverses the effect of food deprivation upon fluid intake in mice. Anita. Behav. 15: 402-408, 1967. 6. Fusco, M., R. L. Malvin and P. Churchill. Alterations in fluid electrolyte and energy balance in rats with median eminence lesions. Endocrinology 79: 301-308, 1966. 7. Kakolewski, J. W. and E. Deaux. Aphagia in the presence of drinking an isosmotic NaCI solution. Physiol. Behav. 8: 623-630, 1972. 8. Kutscher, C. L. Incidence of food-deprivation polydipsia in the white Swiss mouse. Physiol. Behav. 7: 395-399, 1971. 9. Kutscher, C. L. Genetic variation and the intake of sucrose, saccharin, and sodium chloride solutions in mice. Paper presented at the Eastern Psychological Association, Boston, Mass., April 1972. 10. Kutscher, C. L. Strain differences in drinking in inbred mice during ad libitum feeding and food deprivation. Physiol. Behav. 13: 63-70, 1974.

11. Lepkovsky, S., R. Lyman, D. Fleming, M. Nagumo and M. M. Dimick. Gastrointestinal regulation of water and its effect on food intake and rate of digestion. Ant Z Physiol. 188: 327-331, 1957. 12. Naik, D. V. and H. Valtin. Hereditary vasopressin-resistant urinary concentrating defects in mice. An~ J. Physiol. 217: 1183-1190, 1969. 13. Palmieri, G. M. A. and S. Taleisnik. Intake of NaCl solution in rats with diabetes insipidus. J. comp. physiol. Psychol. 68: 38-44, 1969. 14. Silverstein, E. Primary polydipsia and hydronephrosis in inbred strains of mice. Acta Endocr. Suppl. 51, 1960. 15. Silverstein, E., L. Sokoloff, O. Mickelsel~ and G. E. Jay, Jr. Primary polydipsia and hydronephrosis in an inbred strain of mice. Am. J. PathoL 38: 143-157, 1961. 16. Smith, M. and M. Duffy. Consumption of sucrose and saccha.tin by hungry and satiated rats. J. comp. physiol. PsychoL 5~. 65-69, 1957. 17. Stellar, E., R. Hyman and S. Samet. Gastric factors controlling water, and salt-solution drinlOng. J. comp. physiol. Psychol. 47: 220-226, 1954. 18. Stewart, A. D. and J. Stewart. Studies on syndrome of diabetes insipidus associated with olignsyndactyly in mice. Am. J. Physiol. 217: 1191-1198, 1969. 19. Storer, J. B. Longevity and gross pathology at death in 22 inbred mouse strains. J. Geront. 21: 404-409, 1966. 20. Swarm, H. G. Sodium chloride and diabetes insipidus. Am. J. Physiol. 126: 341-346, 1939. 21. Titiebaum, L. F., J. L. Falk and J. Mayer. Altered acceptance and rejection of NaCI in rats with diabetes in$ipidus. Am. J. PhysioL 199: 22-24, 1960.