The control of water and sodium chloride intake by postingestional and orosensory stimulation in water-deprived rats

We investigated the role of oropharyngeal and postingestional stimulation in the control of the intake of water and NaCl solutions by testing water-deprived rats under real- and sham-drinking conditions with water, 0.150, 0.225, and 0.300 M NaCl solutions. A series of real-drinking tests was given until intake stabilized followed by a series of sham-drinking tests with the same solution. When sham intake stabilized the concentration was increased and the series of real- followed by sham-drinking tests was repeated. Intake of water and 0.150 M NaCl in the first sham-drinking test was significantly greater than in the preceding real-drinking test and did not change with real- or sham-drinking experience. In contrast, intake of 0.225 and 0.300 M NaCl in the first sham-drinking test was not significantly greater than in the preceding real-drinking test but increased with sham-drinking experience. Real intake of 0.225 and 0.300 M NaCl following sham-drinking experience with a lower concentration declined significantly with real-drinking experience. These results show that postingestional stimulation plays a direct role in the control of the intake of water and isotonic saline with little or no orosensory contribution. In contrast, conditioned orosensory responsiveness played the central role in the control of the intake of the two hypertonic solutions with little or no direct contribution from postingestional stimulation. Postingestional stimulation, however, played an indirect role by serving as the unconditioned stimulus for the conditioned orosensory control.     

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.     

Stimulation of insulin release and suppression of feeding by hepatic portal glucagon infusion in rats

Plasma insulin and glucose concentrations were measured in rats by remote blood sampling techniques 5 and 25 min after the start of a continuous intraportal glucagon infusion (0.33, 1.0, 3.3, 10 and 33 micrograms/kg/min). Plasma insulin levels were elevated in a dose-related fashion by glucagon, with the highest dose producing a 23-fold increase above control levels. In contrast, the glycemic effect of glucagon was not dose-related. Glucagon-induced hyperglycemia was similar for all glucagon doses, despite the fact that a glucagon dose range spanning two orders of magnitude was used. In a second experiment, plasma glucose and insulin were measured as described above at two glucagon infusion rates (1 and 10 micrograms/kg/min), but the animals were allowed to eat during the infusion. Results showed that the effects of glucagon infusions on plasma insulin and glucose were additive with the normal prandial changes in these substances. Finally, food intake was inversely related to insulin level and dissociated from the hyperglycemia during glucagon infusion. These results show that exogenous glucagon provides a potent stimulus for insulin release in the rat both in the presence and in the absence of food. Furthermore, these results in combination with other data suggest that glucagon-induced hyperinsulinemia merits further investigation as one possible determinant of glucagon satiety in the rat.     

Effects of subcutaneous administration of the gamma-aminobutyric acid(A) receptor agonist muscimol on water intake in water-deprived rats

The effects of the gamma-aminobutyric acid(A) (GABA(A)) receptor agonist muscimol were investigated on water intake in rats that had been deprived of water for 16 h. Muscimol (0.5-2.0 mg/kg sc) produced a dose-related inhibition of water consumption in both male (n=8) and female (n=8) rats, with maximal suppression of drinking occurring during the first 30 min after administration. Doses of 1 and 2 mg/kg produced significant decreases in water intake (P<.01), while a lower dose of 0.5 mg/kg was without effect. The hypodipsic effect of muscimol (1.0 mg/kg sc) was abolished by pretreatment of the animals with the GABA(A) receptor antagonist bicuculline (1 mg/kg sc). Furthermore, muscimol (2 mg/kg sc) did not produce aversion in a two-bottle conditioned taste aversion test, indicating that the suppressant effects of muscimol on water intake are not due to drug-induced malaise. The results suggest that systemic administration of muscimol produces a behaviourally specific suppression of primary drinking in rats by a GABA(A) receptor-mediated mechanism. Moreover, this action of muscimol appears to be independent of the gender of the animals.     

Effects of hepatic portal infusion of hypertonic saline on glucagon response to exercise.

The present study was conducted to evaluate the influence of a hepatic portal infusion of hypertonic saline on the metabolic and hormonal responses to exercise. Adrenodemedullated male rats were studied at rest or after 30 min of treadmill exercise (26 m/min, 0% grade). Three groups of rats were infused continuously at a rate of 52 microL/min with one of the following randomly assigned conditions: hypertonic 3.6% NaCl (P3.6% NaCl) or 1.8% NaCl (P1.8% NaCl) infused into the hepatic portal vein, and hypertonic 3.6% NaCl (J3.6% NaCl) infused into the jugular vein. One group of rats received no infusion (SHAM). The infusions of hypertonic NaCl into the portal or the jugular site resulted in a significant (p < 0.05) increase in peripheral concentration of Na+, Cl-, and osmolality at rest and after exercise. The antidiuretic hormone (ADH) concentration was significantly (p < 0.05) increased by the P3.6% NaCl and J3.6% NaCl infusions at rest and after exercise. Exercise caused a significant (p < 0.05). decrease in liver glycogen content, peripheral and portal plasma glycemia, and insulinemia regardless of the different types and sites of infusions. However, the peripheral glucagon response to exercise was significantly (p < 0.05) increased only when hypertonic saline (1.8 or 3.6%) was infused into the portal vein. Portal and peripheral lactate concentrations at rest and after exercise were significantly (p < 0.01) higher in P3.6% NaCl than in all other groups. It is concluded that a 30-min hypertonic saline infusion into the hepatic portal vein does not specifically influence the insulin response at rest and after exercise, but that glucagon response to exercise is increased by such an infusion.     

Effect of continuous vasopressin infusion on circadian rhythms of food and water intake,diuresis, and electrolyte excretion in brattleboro rats

Department of Physiology, Medico-Biological Research Institute, Bulgarian Medical Academy, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 109–111, February, 1990.     

Access rate as a determinant of sucrose or water preference in water-deprived rats

Water-deprived rats' licking on either of two discs was reinforced on a fixed interval 19-sec schedule involving successive choices between 6.2 μl drops of 8% sucrose solution and water. Three of 5 rats showed a water preference whereas the remaining two exhibited a position preference. For rats that preferred water, increasing the number of continuously reinforced licks at the end of each fixed interval from 1 to 40 or decreasing the fixed-interval from 19 to 0.25 sec (one reinforcement/interval) reversed preference from water to sucrose solution. It was concluded that with highly restricted accessibility to 8% sucrose solution and water during successive tests, a decrease in access rate can reverse preference from sucrose solution to water independently of the quantity of fluid consumed.     

Effect of intracerebroventricular deuterium oxide on water intake and AVP release induced by intravenous infusion of angiotensin II in sheep

The effect of intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of deuterium oxide (D2O), with NaCl added to isotonicity, on the water intake and arginine vasopressin (AVP) release caused by intravenous (i.v.) infusion of angiotensin II (AII) (4.8 nmol min-1) was studied in euhydrated sheep. The i.c.v. infusion of D2O, which started 80 min before commencement of the AII infusion, induced a water diuresis in four out of six animals and a measurable decrease in plasma AVP concentration. The i.v. infusion of AII effectively stimulated the AVP release and the response was unaffected by prior and simultaneous i.c.v. administration of D2O. However, the water intake measured 2 min after cessation of the AII administration was reduced by 50% when D2O was infused i.c.v. compared to that seen after simply the AII infusion. The inhibitory effect of D2O on AII-induced drinking disappeared rapidly after discontinuation of D2O administration. Compensatory increased drinking was seen during the first post-infusion hour, resulting in an equivalent cumulative intake of water at 60 min post-infusion in the two types of experiments. The present results support the idea that at least some of the cerebral effects of circulating AII on fluid balance are medicated via targets which are simultaneously accessible to influences from the blood and the cerebrospinal fluid.     

Effects of catecholamines on water intake in rats

It is known that intraperitoneally (IP) injected adrenaline (A) inhibits food intake in otherwise hungry animals. In a recent work, Hinton et al. (6) showed that IP A also inhibits water intake in thirsty rats, concluding that A's effect is unspecific. We administered A IP or intramuscularly (IM) in different doses in rats made thirsty either by 18-h water deprivation or by subcutaneous injection of hypertonic saline or polyethylene glycol. IP A reduced water intake in all experimental conditions. A dose-related inhibition was observed in water-deprived animals. On the other hand, IM A showed a small effect only at the highest dose (50 micrograms/100 g body weight). When some of these experiments were repeated using noradrenaline (NA) and isoproterenol (IS), IM administration of either substance showed no effect. IP administration reduced water intake significantly only at the highest dose of NA (50 micrograms/100 g). It is concluded that water intake inhibition by catecholamines in rats made thirsty either by osmotic or by volumetric challenges is of porto-hepatic origin and, in contrast with food intake inhibition, has no beta-adrenergic component.     

Estrogen influences stimulated water intake by ovariectomized female rats

To further elucidate the influence of estrogen on water consumption, we examined water intake by adult female rats stimulated by water deprivation, injection of hypertonic saline or injection of isoproterenol (ISOP), a beta-adrenergic agonist that activates the renin-angiotensin system (RAS). Rats were ovariectomized (OVX) then injected with estradiol benzoate (EB; 10 microg/0.1 ml oil) or the oil vehicle (OIL; 0.1 ml) for 2 consecutive days. Twenty-four hours after the second injection, rats were deprived of food and water. On the following day, rats were given water and intake was measured after 2 h. EB significantly decreased water intake compared with that by OIL-treated rats following water deprivation. Two additional groups of adult female rats were OVX and treated with EB or OIL. Forty-eight hours after EB or OIL treatment, rats were injected with hypertonic saline (1 ml of 2 M NaCl) or ISOP (30 microg/kg in 0.15 M saline) and water intake was measured after 2 h. EB significantly attenuated water intake following ISOP but not after hypertonic saline. Finally, we examined plasma sodium concentration (pNa) after hypertonic saline and plasma renin activity (PRA) after ISOP in EB- and OIL-treated rats and found no differences in pNa or PRA. These results suggest that the stimuli for water intake after hypertonic saline and ISOP were comparable in EB- and OIL-treated rats. Taken together, these results raise the possibility that EB attenuation of stimulated water intake is specific to water intake elicited by activation of the RAS.     

Effects of continuous intramesenteric infusion of glucose and amino acids on food intake in rats.

Prolonged infusions of various fluids at a rate of 21 ml/23.5 hr through the mesenteric vein and the vena were performed on rats and effects on ad lib food intake were determined. Results indicate that continuous intramesenteric infusion of 5–10% glucose solutions or a 5% Aminofusin L solution suppresses food intake. No effects were observed when solutions were infused via the caval vein. A 10% solution of 3-O-methyl-d-glucose did not affect food intake when introduced by either route. These data support directly the presence of glucose and amino acid receptive mechanisms in the portohepatic system involved in the control of food intake.     

Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade.

The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.     

Modulation of daily water intake by dopamine in caudate and accumbens nuclei in rats.

Bilateral lesions of accumbens and caudate nuclei resulted in significant and sustained increase in water intake. Administration of different doses of dopamine (DA) into these nuclei facilitated a dose-dependent increase in 24-h water intake, whereas injection of spiperone following administration of DA inhibited DA-facilitated water intake in a dose-dependent manner. Conversely, administration of DA and spiperone did not elicit any change in water intake in septal nuclei; rather septal lesion facilitated the water intake. This suggests that the nucleus accumbens and nucleus caudatus act as facilitatory thirst areas and that DA is a possible dipsogenic neurotransmitter in these nuclei. This also suggests that the nucleus septal lateralis is a thirst-inhibiting centre where DA may not be involved in dipsogenesis.     

Effect of phenazepam on ethanol intake in rats

The new Soviet transquilizer phenazepam, if given by daily intraperitoneal injection to rats in a dose of 1 mg/kg for 3 weeks, can depress the craving for ethanol developed beforehand by administration of a 5% solution of alcohol for 2 months as the only source of fluid. The mechanism of this effect is probably connected with changes in the activity of the hypothalamic neurosecretory centers observed under these conditions. The property thus revealed evidently also explains the efficacy of phenazepam in the treatment of patients with chronic alcoholism.Laboratory of Pharmacology of the Nervous System and Laboratory of Drug Toxicology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 32–35, July, 1979.     

The effect of intravenous infusion of antidiuretic hormone on water intake in the rat

1. In rats the continuous I.V. infusion of ADH at rates up to 6.0 mu. kg(-1) min(-1) decreased drinking caused by water deprivation, by a 10% increase in osmotic pressure, and by caval ligation.2. Infusion of ADH at rates between 0.07 and 6.0 mu. kg(-1) min(-1) never potentiated drinking nor did it significantly affect the 24 hr water intake of rats that were in water balance at the start of the experiment.3. Urine output was slowed by a rate of infusion (13.0 muu. kg(-1) min(-1)) which was approximately 150 times smaller than the lowest rate which was found to decrease water intake.4. Since the rates of infusion of ADH which directly affect water intake and urine flow are so different, it is unlikely that ADH is a general homoeostatic hormone which controls both thirst and urine output in the rat.     

Control of water intake in thermally dehydrated rats

Male rats were thermally dehydrated by exposure without water to an environmental temperature of 40 degrees C for 0-4 hr or to environmental temperatures of 25-40 degrees C for 4 hr. Water intake was then measured for 2 hr or a blood sample was taken to determine the effect of heat exposure on body water status. Evaporative water loss and water intake increased with increased duration and severity of heat exposure. Heat exposure significantly increased plasma osmolality and plasma sodium concentration and significantly decreased plasma potassium concentration. Hematocrit and plasma protein concentration increased slightly but not significantly with heat exposure. The increases in water intake in association with increases in evaporative water loss, plasma osmolality and plasma sodium concentration with no significant increases in hematocrit or plasma protein concentration indicates that the thirst induced by thermal dehydration is primarily osmotic in nature. Water intake equal to about 50% of the evaporative plus urinary water loss reduced plasma osmolality and sodium concentration to control levels, removing the stimulus to drink before the water loss was replaced.