Effect of potassium depletion on mineral appetite in the rat.

Studied potassium appetite in normal female Sprague-Dawley rats and in rats in which the total body potassium had been reduced by 15-20%. Potassium depletion resulted in increased ingestion of solutions of NaCl, KCl, CaCl2, and quinine sulphate in concentrations that were unacceptable to normal Ss. The amount of potassium ingested was related to the degree of potassium depletion and repletion was usually completed within 24 hr. when potassium was offered. Potassium-depleted Ss also drank large quantities of aversive concentrations of sodium chloride. This was preferred to potassium chloride and its ingestion appeared to be unrelated to need. The appetite state was reversed by prior intragastric repletion with potassium but not with sodium salts. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of deoxycorticosterone-induced sodium appetite on hedonic behaviors in the rat.

The authors tested the hypothesis that chronic treatment with a dose of deoxycorticosterone acetate (DOCA) known to elicit a robust sodium appetite can negatively affect the hedonic state of rats. Daily treatment with DOCA with no opportunity to ingest saline produced a rightward shift in the midpoint (effective current 50) of lateral hypothalamic self-stimulation (LHSS) current-response functions and reduced intakes of a palatable sucrose solution. Providing rats with 0.3 M saline during DOCA treatment prevented the rightward shift in LHSS response functions and the decrease in sucrose intake. The authors concluded that a chronic sodium appetite, with no opportunity to attenuate the appetite, can elicit a reduced responsiveness to reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prior episodes of sodium depletion increase the need-free sodium intake of the rat.

Prior episodes of sodium depletion increase the daily 3% NaCl intake of rats. They ingest large volumes and continue to do so for as long as 3 months after recovery from sodium deficit while eating sodium-rich food and while plasma sodium concentration and renal function are normal. The increased daily intake of sodium is, therefore, need-free. There is a marked sex difference in the need-free intake of 3% NaCl. Female rats drink more salt than do male rats when they are sodium replete and depletion naive. Repeated depletions raise the need-free intakes of both sexes but the effect is greater in females. Plasma concentrations of angiotensin II and aldosterone, which are markedly elevated by each episode of sodium depletion, return to basal levels between and after depletions, and are not the cause of the chronically increased need-free salt intake of the multi-depleted rat. These results suggest that the persistent increase in daily 3% NaCl intake that occurs in the rat with a history of repeated sodium depletions is a permanent, nonpathological increase in avidity for the taste of salty substances that results in life-long overconsumption of salt. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of the ionic specificity of sodium appetite in the rat pup

Sodium-deficient adult rats prefer NaCl to other monochloride salts (e.g., Denton, 1991; Schulkin, 1991). However, it is not known when or how this specificity develops. Our experiments charted the development of the ionic specificity of sodium appetite aroused by sodium depletion or intracerebroventricular injection of renin. We compared intake of 3% NaCl to three other monochlorides, potassium (K), ammonium (NH4), and lithium (Li), and calcium chloride (CaCl2) at various ages between 72 hr postnatal and weaning. This revealed a biphasic developmental scheme: The adult pattern of discrimination between the salts emerges between 3 and 18 days of age. Subsequently, the preference for Na over the other salts increases into adulthood.     

Sodium appetite elicited by intracerebroventricular infusion of angiotensin II in the rat: I. Relation to urinary sodium excretion.

Previous results show that icv infusion of angiotensin II (Ang II) elicits a substantial sodium appetite in the rat. The present study, with male Sprague-Dawley rats, demonstrated that this phenomenon consists of a small, early phase of sodium ingestion that is not the result of prior sodium loss but that thereafter urinary excretion of sodium exceeds intake and consequently the animals become hyponatremic and hypovolemic. The larger and more sustained bouts of sodium ingestion occurring 8–22 hrs after the start of the Ang II infusion appear to represent a behavioral compensation for this incurred sodium deficit. Results confirm the arousal of a sodium appetite by action of Ang II on the brain but indicate the need for caution in assigning to it a direct and exclusive role in the neuroendocrine control of sodium intake. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat.

Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal-intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine and sodium appetite: Antagonists suppress sham drinking of NaC1 solutions in the rat.

Sodium (Na) ingestion in rats depleted of Na is a strong, motivated behavior that is enhanced further when depleted rats are sham drinking. Dopamine plays a critical role in motivation, including reward associated with consumption of palatable tastes. The present studies assessed the role of dopamine in real and sham drinking of NaCl solutions after Na depletion with the diuretic furosemide (10 mg/kg). Dopamine (D2) receptor antagonists were evaluated (Haloperidol [0.1 mg/kg] and raclopride [0.2 mg/kg]), for their effects on 2 sham and real drinking of 0.3 M NaCl. Sham drinking was markedly reduced by both antagonists whereas real drinking was unaffected. These effects did not appear to be due to malaise or suppression of motor behavior because drug-treated animals were able to increase ingestion substantially when offered less concentrated NaCl (0.1 M). These results suggest that the positive motivating properties of NaCl stimulation in depleted, sham-drinking rats are mediated by central D2 receptors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Formalin-like sodium appetite and thirst elicited by a conditioned stimulus in rats.

Describes 3 experiments with male Wistar rats (N = 33) in which the intake of water and a .33-M NaCl (saline) solution was elicited by a stimulus which was previously associated with the administration of formalin, and hence with a physiological need for both water and sodium. This "conditioned" thirst and sodium appetite were not due to a water or sodium need, however, and in fact were shown to be the result of pseudoconditioning. Results are interpreted as being consistent with a hypothesis that a physiological need must be present in order for conditioned appetitive behavior to be manifest. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased sodium appetite and thirst in rat induced by the ingredients of liquorice, glycyrrhizic acid and glycyrrhetinic acid

In the rat, blocking 11 beta-OHSD with the active ingredient of liquorice, glycyrrhizic acid (GZA) or its hydrolytic product, 18 beta-glycyrrhetinic acid (GTA), caused potassium loss, increased water intake and a primary increase in salt appetite that was specific for sodium and not secondary to sodium loss. Intracerebroventricular injection of angiotensin II enhanced the sodium appetite but carbachol did not. The stimulating effects of GZA or GTA on intakes of water and NaCl resembled those caused by the administration of excessive amounts of mineralocorticoid. The results suggest that GZA- or GTA-induced drinking behaviour is mediated by circulating glucocorticoids. After liquorice blockade of 11 beta-OHSD, the peripheral and central mineralocorticoid receptors are no longer protected from glucocorticoid action.     

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 1 st 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. (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)     

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)     

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)     

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)     

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)     

Reversible colchicine-induced disruption of amygdaloid function in sodium appetite

Bilateral injections of the antimitotic drug colchicine into the medial amygdaloid nuclei resulted in a dissociation of the normally concurrent sodium appetite and water thirst in rats following formalin-induced hypovolemia and hyponatremia. While control rats drank the normally aversive sodium solution as well as water after formalin injection, colchicine-treated animals failed to ingest the sodium solution but did consume the expected amount of water in order to compensate for hypovolemia. Sodium consumption, but not water consumption, remained significantly depressed in the colchicine-treated rats when they were challenged again with formalin 11 days but not 20 days after amygdaloid injections. The latter result suggested complete recovery from the colchicine-induced amygdaloid dysfunction. This study indicates that colchicine may serve as a potentially useful technique for producing reversible lesions of known duration for the assessment of brain-behavior relationships.     

Self-administered intravenous infusion of hypertonic solutions and sodium appetite of sheep.

Studied the effects of self-administered iv infusion of hypertonic NaCl, mannitol, glucose, urea, or isotonic NaCl on Na appetite. 22 Merino-Cross sheep were trained to barpress to replace Na deficits of 300–500 mmol. During basal conditions, each delivery to a drinking cup was 15 ml of .6 M NaHCO? (9 mmol). In the experimental situation, an iv infusion was given automatically with each delivery to the drinking cup. Ingestion of NaHCO? solution was significantly reduced by all hypertonic solutions, the largest decrease being caused by hypertonic NaCl or mannitol. The decreased intake was observed within 10 (with infusion of hypertonic NaCl, mannitol, or glucose) or 20–40 (with urea infusion) minutes, irrespective of whether water was concurrently available to drink. At 20 min, plasma Na was increased by hypertonic NaCl, decreased by mannitol or glucose, and not changed by urea. CSF Na concentration was increased by all hypertonic solutions. In regard to the "turn-off" of Na appetite by systemic infusion, data are consistent with the theory of neural cells within the blood–brain barrier responsive to changes of Na concentration or osmolality in their environment. In contrast, water intake was stimulated by hypertonic NaCl or mannitol but not by urea or glucose. Results suggest that the sensors involved in thirst (e.g., osmoreceptors) are in an area of the brain lacking the blood–brain barrier. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chloride depletion and hypochloraemia as a cause of renal sodium and water loss in the rat

1. To study the effects of chloride depletion, without sodium depletion or change in plasma tonicity, on renal excretion of sodium and water, a single exchange peritoneal dialysis was performed in rats against a solution of glucose (15 g/1) containing either NaCl (150 mmol/l, control) or NaHCO3 (150 mmol/l, experimental); KHCO3 (4mmol/l)was added to both solutions. All rats were prepared before dialysis by a low NaCl diet for 10 days. 2. Peritoneal dialysis against NAHCO3 consistently produced a negative sodium and water balance compared with dialysis against NaCl. Despite this, subsequent electrolyte balance for 3 days showed that chloride-depleted rats excreted significantly more sodium and water and had a reduced urinary osmolality as compared with control animals. Increased sodium and water loss were unexplained by osmotic or bicarbonate diuresis. Kaliuresis was seen in the chloride-depleted rats but muscle potassium was not significantly depressed. 3. With sodium and water loss and continued renal chloride conservation, plasma chloride rose on the average from 88 mmol/l after dialysis against NaHCO3 to 100 mmol/l (control 104 mmol/l) at 72 h. Concomitant with this increase in plasma [C1-], on the third day after dialysis, during hydropenia, urinary osmolality and papillary [Na+] were not different from control cencentrations. 4. It is postulated that chloride depletion and/or hypochloraemia leads to diminished chloride transport in the loop of Henle and that this causes reduced sodium transport into the medulla, impaired concentration ability and inappropriate urinary sodium loss.     

Intraventricular neuropeptide Y decreases need-induced sodium appetite and increases pica in rats.

Neuropeptide Y (NPY) is a potent endogenous stimulator of food intake. In addition to stimulating increased food intake, when paired with a novel-flavored solution, NPY produces an aversion to that flavor. Hence, exogenous NPY elicits 2 seemingly opposing behaviors, increased feeding and the formation of a conditioned taste aversion. One interpretation of these data is that NPY produces some form of malaise or visceral illness. NPY's orexigenic and malaise-inducing properties were tested in rats with 2 measures sensitive to malaise, increased kaolin consumption (pica behavior) and failure to express need-induced sodium intake. Administration of NPY resulted in increased food intake, increased kaolin consumption, and decreased need-induced sodium intake. These data support the hypothesis that exogenous NPY has both orexigenic and malaise-inducing properties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)