Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite.

Our laboratory has reported that manipulations that provoke a robust sodium appetite (e.g., sodium depletion, deoxycorticosterone acetate) decrease lateral hypothalamic self-stimulation (LHSS) reward if rats are denied access to hypertonic saline solutions. The following studies investigated the interaction between chronic sodium appetite and the renin-angiotensin-aldosterone system on LHSS reward. In Experiment 1, animals treated with the diuretic furosemide (20 mg/kg) when denied access to saline exhibited an increase in the current required to produce 50% of the maximum LHSS response rate (ECu50) 48 hr after extracellular volume depletion. Furosemide-depleted rats that were allowed to drink 0.3 M saline after depletion, or that were treated with the selective mineralocorticoid receptor (MR) antagonist spironolactone, which significantly reduced sodium appetite, did not show ECu50 changes. In Experiment 2 chronic intracerebroventricular administration of the selective MR antagonist RU 28318 (10 μg/μl/hr) prevented decreases in the ECu50 induced by deoxycorticosterone acetate-no salt treatment. We conclude that an unresolved sodium appetite will reduce responding for rewards and that experimental manipulations that reduce sodium appetite (e.g., access to saline or blockade of MR) decrease hedonic deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic immobilization stress reduces sodium intake and renal excretion in rats

The influence of chronic exposure to immobilization (IMO) on sodium appetite as well as sodium and potassium renal excretion in adult male Wistar rats was studied. The animals were individually housed and all variables under observation were measured in metabolic cages the first, seventh, and thirteenth days once the experiment had started. Half of the rats had access to water, and the remainder of the rats had access to both water and saline solution (1.5% NaCl). IMO reduced the intake of saline solution. Renal water, sodium, and potassium excretion in those IMO rats having access to saline were lower than in control rats. The effects of IMO were very similar during all observation days; therefore no evidence of adaptation to repeated stress was found. The present data indicate the following: (i) IMO stress reduced sodium appetite, probably as a secondary effect to the deficit in sodium renal excretion; (ii) IMO caused antidiuresis and antikaliuresis, only in those rats taking saline solution; (iii) no adaptation to repeated IMO stress was found in any of the tested variables. The reduction of sodium appetite observed in stressed rats might be a homeostatic mechanism to maintain sodium balance after impairment of renal sodium excretion caused by stress.     

Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes

INTRODUCTION: An increase in digitalis-like substances has been reported in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that the role of saline and unilateral nephrectomy in DOCA hypertension may be due to stimulation of endogenous digitalis-like substances. METHODS: We investigated the effects of digoxin and DOCA alone and in combination in intact rats drinking water. Forty male Sprague-Dawley rats were used (body weight 223-298 g). RESULTS: Neither digoxin (40 micrograms/kg per day, by gavage, for 35 days, n = 10) nor DOCA (30 mg/kg twice a week, subcutaneously, for 5 weeks, n = 10) caused a consistent increase in blood pressure in intact rats drinking water. In contrast, combined digoxin and DOCA administration (n = 10) increased systolic blood pressure from day 18 of treatment onwards, to a maximum at day 34 compared with sham-treated rats (n = 10). There were no consistent changes in water intake, urine volume, urinary sodium or potassium excretion, or plasma sodium or potassium concentration with digoxin treatment. DOCA increased water intake and urine volume, and caused an initial decrease in urinary sodium excretion, but no change in urinary potassium excretion or plasma sodium concentration. Plasma potassium excretion was lower in DOCA- than sham-treated rats. CONCLUSION: Combined digoxin and DOCA administration in intact rats drinking water increased blood pressure significantly compared with either drug alone, raising the possibility that the mechanism by which nephrectomy and salt loading contribute to DOCA hypertension in the rat might be through stimulation of endogenous digitalis-like substances.     

Interaction of hydration and subfornical organ lesions in sodium-depletion induced salt appetite.

The authors tested whether the level of hydration after furosemide diuresis and 22 hrs of sodium depletion affects the amount of water or 0.3 M NaCl solution consumed by rats with intact brains or with lesions of the subfornical organ (SFO). Rats received 2 (underhydrated) or 10 (euhydrated) ml/kg water by gavage as the only fluid input 2, 4, and 20 hrs after 10 mg/kg furosemide. These hydration treatments had little or no effect on the amount of saline consumed in 2 hrs by intact rats. SFO lesions reduced water intake regardless of hydration condition. Euhydrated, SFO-lesioned rats drank a normal amount of saline, but underhydrated, lesioned rats drank less saline than any other group. Thus, euhydration may facilitate salt appetite in SFO-lesioned rats, and the deficits in salt appetite noted in SFO-lesioned rats may result from deficits in water ingestion rather than from a destruction of angiotensin II receptor sites that directly provoke salt appetite. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Angiotensin and salt appetite: Physiological amounts of angiotensin given peripherally increase salt appetite in the rat.

In 2 experiments, adrenalectomized male Sprague-Dawley rats were maintained ad lib on distilled water, 3% saline, and sodium-free food. In Exp I, 45 Ss were given desoxycorticosterone acetate (DOCA [.1–2 mg/kg/day, intramuscularly]) for 5 days to determine the dose of DOCA that would produce the lowest voluntary saline intake, and 800 μg/kg/day was found to produce the nadir in saline intake. In Exp II, 40 Ss were placed ad lib on distilled water, saline, and sodium-free food as described above, maintained on 800 μg/kg/day DOCA, and infused with 4, 25, or 100 μg/kg/day angiotensin II (AII) or 0.9% saline. The 3 AII groups showed significant percentage changes in their saline intake above pre-AII levels; the saline control group showed no change in saline intake from pre-AII level. Results demonstrate the production of salt appetite in rats by peripheral administration of physiological doses of AII. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus.

Angiotensin receptors in the most ventral part of the ventral median preoptic nucleus (VVMnPO) or organum vasculosum laminae terminalis appear to be important for salt appetite to angiotensin in rats. If so, then small lesions of this region should reduce salt appetite that is dependent on angiotensin. In separate experiments, the lesion greatly reduced salt appetite after treatments with chronic oral captopril or sodium depletion. On the other hand, the VVMnPO lesion actually enhanced salt appetite to deoxycorticosterone acetate. The lesion did not affect water intake to water deprivation, combined food-water deprivation, isoproterenol, or hypertonic saline, and basal plasma osmolality and sodium values were normal. These experiments suggest that VVMnPO lesions selectively affect angiotensin-induced salt appetite without producing the gross hydrational deficits that occur with larger lesions of the ventral forebrain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory effects of estrogen on stimulated salt appetite in rats.

Adult male rats consumed 50–250% more 0.5 M NaCl solution than females did during a 7-hr drinking test when robust salt appetite was elicited by dietary sodium deprivation for 8 days, daily injections of deoxycorticosterone, or adrenalectomy followed by 2 days of sodium deprivation. In contrast, male rats drank much less saline after systemic treatment with the natriuretic agent furosemide, adrenalectomy followed by 1 day of sodium deprivation, or subcutaneous/ly (sc) treatment with colloid solution after 2 days of sodium deprivation, and female rats drank comparably small volumes. Conversely, 30-day-old prepubescent male and female rats showed equally robust salt appetites after 8 days of sodium deprivation. These and other findings support an inhibitory role of estrogen on salt appetite in rats, which appears to occur only when the appetite is especially pronounced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura et al, see record 84-21706) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thirst and sodium appetite after colloid treatment in rats with septal lesions.

Previous experiments in which angiotensin II (AII) and mineralocorticoids were administered to rats have suggested that these hormones play a natural role in mediating thirst and sodium appetite. This hypothesis was examined by making use of 20 male Sprague-Dawley rats with septal lesions, which have an apparent sensitivity to the central effects of AII, and by studying their behavioral response to sc treatment with 5 ml of a 30% polyethylene glycol solution, which produces hypovolemia and thereby stimulates the secretions of renin and aldosterone. The induced thirst and sodium appetite both were markedly enhanced in the brain-damaged Ss. However, water intake was not increased when the hypovolemia was moderate, and sodium appetite was augmented only when Ss had been sodium deprived, a procedure known to potentiate aldosterone secretion. Findings support suggestions that while AII normally contributes little to thirst, it may help to mediate sodium appetite in rats when aldosterone is abundant. The 2 drives were not elicited uniformly; those Ss that drank the most water after colloid treatment consumed the least saline. While septal lesions may sensitize the rat's brain to the sodium-appetite-eliciting effects of AII as well as to its dipsogenic effects, sodium appetite may emerge only if the induced thirst is not too pronounced. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of salt intake, ANG II synthesis and SFO lesion on thirst and blood pressure during sodium depletion. Subfornical organ

Water intake was elevated in sodium-depleted rats during a daytime salt appetite test, but other rats drank a similar amount of water when saline was not available for drinking during the test. This water intake stimulated by sodium depletion was blocked by an inhibition of angiotensin (ANG) II synthesis with a high dose of captopril (100 mg/kg, sc). Captopril did not reduce water intake by causing hypotensive shock or uremia, because water and saline intakes were increased rather than decreased after a low dose of captopril (5 mg/kg) that also reduced blood pressure and elevated blood urea nitrogen. The water intake, but not salt appetite, induced by sodium depletion was greatly reduced by a lesion of the subfornical organ (SFO) in one-bottle tests, and this was not clearly related to any effects of the lesion on blood pressure. A physiological role for ANG II in water intake induced by sodium depletion has recently been disputed, but the simplest explanation for the data remains that elevated levels of circulating ANG II bind to receptors in the SFO to generate daytime water drinking during sodium depletion.     

Thirst and sodium appetite after colloid treatment in rats.

In 3 experiments with male albino Sprague-Dawley rats, injection of polyethylene glycol (PEG) solution (10–30% solution) produced a progressive sequestration of extracellular fluid at the injection site. PEG-treated Ss showed both thirst and sodium appetite. However, water intake began 1–2 hrs after the injections, whereas consumption of NaCl solution did not start until 3–4 hrs later. Then Ss ingested both fluids alternately until plasma volumes were restored, whereupon saline intake became even more prominent and water was consumed due to induced osmoregulatory needs. These 3 phases were seen regardless of the dose of PEG or the concentration of saline. After maintenance on a sodium-deficient diet for 2–4 days or after bilateral adrenalectomy, Ss increased their intake of saline immediately after PEG treatment. Findings suggest that the delayed onset of sodium appetite after PEG treatment that occurred when Ss were maintained on standard sodium-rich chow resulted from the buffer provided by surplus extracellular fluid in those Ss. They further suggest that sodium appetite may be stimulated by a decreased availability of sodium in the brain. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sodium appetite in adrenalectomized rats following dietary sodium deprivation.

Experimented with operated, sham-operated, and comparison male Sprague-Dawley rats (N = 74). Adrenalectomized (Adrex) rats adjusted well during adrenal insufficiency when saline solutions were available. Despite continuous uncontrolled losses of relatively large amounts of sodium in their urine, they managed to maintain body fluids at approximately normal levels by replacing crucial sodium losses, if only temporarily, through frequent intakes of saline. It is concluded that the threshold for sodium appetite in Adrex rats is associated with relatively small sodium deficits, and roughly similar deficits also are effective in stimulating sodium appetite in intact Ss. When more pronounced losses result from maintenance on a sodium-free diet, Adrex Ss rapidly drink more than enough saline to replace their deficits. Thus, it seems evident that mineralocorticoids need not have a vital role in either the initial salt-drinking response of intact Ss to minor sodium deficits or their overcompensation for moderate sodium deficits. (32 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clonidine-induced antagonism of norepinephrine modulates the attentional processes involved in peak-interval timing.

The effects of the α2-agonist clonidine and the α2-antagonist idazoxan were studied with emphasis on the attentional mechanisms subserving interval-timing behavior. Administration of clonidine (0.015 mg/kg IP) to rats trained on a 20-s peak-interval (Pl) timing procedure caused a rightward shift in peak functions, whereas idazoxan (0.15 mg/kg IP) caused a leftward shift. Rats were also trained on 10-s and 30-s baseline Pl timing procedures in combination with the prior-entry and prior-entry reversal versions of this task that produced leftward shifts and rightward shifts relative to baseline training, respectively. Clonidine (0.075 mg/kg IP) produced a rightward shift in peak functions for all of these behavioral procedures. Taken together, thcsc horizontal shifts in the peak functions indicate a decrease (leftward shift) or an increase (rightward shift) in the latency to start the internal clock that is influenced both by the attentional demands of the task and the effective level of brain norepinephrine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sodium appetite in lactating rats.

Lactating rats that were given free access to sodium-deficient food, water, and 0.51 M NaCl solution showed no evidence of sodium appetite. The estimated daily loss of 1–2 mEq Na in milk was replaced by basal daily intake of 2–5 ml of saline. Sodium loss in urine was minimal, but milk sodium concentration was unchanged, and pups grew normally. Saline intake was enhanced when lactating rats that had been maintained on standard laboratory chow were injected with 30% polyethylene glycol solution to reduce plasma volume but no more so than when virgin female rats or male rats were similarly colloid-treated. Lactating rats markedly increased their intake of NaCl solution after simply depriving them of dietary sodium for 4 days, whereas male and virgin female rats did not. These findings indicate that pronounced sodium appetite does not invariably accompany lactation in rats, although it can occur whenever such animals become hypovolemic or sodium deficient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoperative sodium experience and hypothalamic lesions in rats.

When a sodium deficit is induced in rats without lesions, they increase their saline intake regardless of prior experience. By contrast, the present experiment with 60 Sprague-Dawley rats found that Ss with lateral hypothalamic lesions increased their saline intake only when they had had preoperative experience ingesting saline in response to a sodium deficit. Ss were given natriuretic and mineralocorticoid treatments to induce sodium appetite. The role of preoperative experience in neural function is discussed. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhanced sodium appetite in rats with lesions centered on nucleus medianus.

Recent experiments have demonstrated that rats with lesions of the ventral portion of nucleus medianus (VNM) frequently exhibit a chronic and robust hyperdipsia, which occurs only at night. The present study demonstrated that the same brain damage may produce a nocturnal appetite for sodium that is similarly pronounced and persistent. Of 68 male Sprague-Dawley rats with VNM lesions, 33 were observed to drink at least 15 ml of 0.51 M NaCl solution per day, and 11 of them consumed more than 30 ml daily. The basis for this high consumption of saline is uncertain; the brain-damaged Ss had normal sodium concentrations, renin activities, and aldosterone levels in plasma during basal maintenance conditions, and they conserved sodium in urine when maintained on a sodium-deficient diet. Nevertheless, the present results indicate that VNM and/or local fibers of passage may play an important role in the control of sodium appetite, as it does in the control of thirst. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Refined salt appetite methodology for rats demonstrated by assessing sex differences.

Describes a refined method for inducing and measuring salt appetite for studying behavioral and neurological functions. The efficiency and reliability of the procedures were demonstrated by parametric studies comparing the appetite behaviors of male and female rats. The method for inducing salt appetite coupled 2 days of dietary sodium deprivation with a brief diuretic treatment. The measurement procedure involved a 2-hr period of access to one of several NaCl solutions differing in palatability or concentration. The induction procedure allowed precise control of drive levels, and the measurement procedure yielded highly reliable results as a function of the properties of the incentives. 32 female mongrel rats consistently ingested about twice as much NaCl solution as did 32 male Ss, regardless of the palatability of the solution or of body sodium levels. At the same time, female Ss lost less sodium in urine following diuretic treatment. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thirst and sodium appetite after colloid treatment in rats: Role of the renin-angiotensin-aldosterone system.

Recent experiments indicated that rats usually develop sodium appetite 5 hrs after sc injection of polyethylene glycol (PEG) solution. However, sodium appetite appeared within 30–60 min if the rats had been maintained on sodium-deficient diet instead of Purina chow for 2–4 days previously. Elevated levels of aldosterone paralleled the appearance of NaCl consumption in both circumstances. In the present experiments, with 65 male albino Sprague-Dawley rats, sodium appetite was no longer potentiated by pretreatment maintenance on sodium-deficient diet when the hypersecretion of aldosterone after PEG administration was prevented by prior hypophysectomy. Conversely, sodium appetite was enhanced in PEG-treated Ss when angiotensin II (AII) was produced in unusually large amounts in the brain, owing to the systemic administration of captopril. This latter effect occurred even when drinking water was withheld and plasma sodium concentrations were markedly elevated. These and other findings raise the possibility that the normal secretion of aldosterone in rats after PEG treatment might permit physiological amounts of AII to be effective in stimulating sodium appetite. Such actions would complement the accepted physiological role of the renin-angiotensin-aldosterone system in the maintenance of blood pressure and sodium balance. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Canine babesiosis in South Africa: more than one disease. Does this serve as a model for falciparum malaria?

The present study was carried out to determine whether the increased salt intake induce by increased specific sodium appetite in pregnant rats modifies water-salt homeostasis throughout pregnancy. Two groups of pregnant rats were used, one fed ad libitum with a normal sodium (NS) diet consisting of standard rat chow and distilled water, and the other fed with a high-sodium (HS) diet with free access to chow, distilled water plus saline solution (1.5% NaCl). Virgin rats in dioestrus were also studied as non-pregnant controls. Pregnant animals were studied on days 4, 9, 14, 20 and 21 of gestation at which time body weight, water and saline intake, sodium excretion, plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) concentrations, as well as plasma osmolality were determined. Data showed that water intake was higher in the NS group, but total fluid intake (water plus saline) was higher in the HS group throughout pregnancy. Dietary sodium intake was the same for both groups but total sodium intake (chow plus saline) was 60-98% higher in the HS rats. Pregnant HS rats excreted more fluid (35-50%) and sodium (up to 100%) compared with NS rats, indicating that the animals could change their renal excretion in response to a 2.5-fold higher dietary sodium intake compared with the control level. Salt satiety during pregnancy did not modify plasma ANP concentration. In both groups of pregnant rats ANP levels increased 3-fold on day 14 without significant alteration in sodium excretion, suggesting that the natriuretic action of ANP is attenuated at least after the second week of pregnancy. High sodium intake did not change plasma AVP concentration or osmolality and both groups showed the same gradual decrease in plasma osmolality (approximately 8 mosmol kg-1) at the end of pregnancy that was not accompanied by decreased plasma AVP concentration. The present data show that rats maintain the special homeostatic equilibrium that occurs in normal pregnancy even when they are allowed to increase sodium intake to satisfy their salt appetite during this period of the reproductive cycle.     

Sodium appetite after transection of the chorda tympani nerve in Wistar and Fischer 344 rats.

Acute sodium depletion in rats leads to dramatic increases in intake of hypertonic NaCl solutions, a behavior known as sodium appetite. The importance of signals conveyed by the chorda tympani (ChT) nerve to the expression of sodium appetite is unclear. The effects of bilateral ChT transection were examined on the short- and long-term response to sodium depletion in Wistar and Fischer 344 (F344) rat strains, because Wistar rats normally display a NaCl preference in the absence of need whereas F344 rats avoid NaCl. In both strains, sodium appetite after ChT transection and treatment with the diuretic furosemide was delayed and blunted or eliminated. The results suggest that signals conveyed by the ChT nerve are important in the expression of a sodium appetite. Effects on F344 rats are particularly interesting because ChT transection surgery appears to have opposite effects on NaCl intake depending on whether F344 rats are sodium replete or deplete. (PsycINFO Database Record (c) 2010 APA, all rights reserved)