Forebrain sites of action for drinking and salt appetite to angiotensin or captopril.

Three-hour infusions of angiotensin II (ANGII) agonists and antagonists were used to determine the relative sites of action of ANG in producing water drinking and salt appetite. In the first experiment, lateral ventricular (LV) but not fourth ventricular (4V) ANG II elicited water and saline intake, and LV but not 4V sarile, a competitive ANG II receptor blocker, reduced saline intake aroused by ip injections of 10 mg/kg furosemide and 6 mg/kg captopril. In the second experiment, water, but not saline, intake to furosemide-captopril treatment was reduced by sarile infusions into the subfornical organ (SFO). It is concluded that (a) brain ANG receptors for water and saline intakes are more accessible from the forebrain than the hindbrain ventricles and (b) receptors for water drinking, but not saline intake, after captopril reside in part in the SFO. Salt appetite appears to be dependent on ANG II receptors somewhere in the forebrain other than in the SFO. (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.     

Impaired drinking responses of rats with lesions of the subfornical organ.

Electrolytic lesions of the subfornical organ (SFO) in rats are known to abolish their drinking response to iv infusion of angiotensin II (AII). Such lesions also attenuate drinking after 20% polyethylene glycol solution (PEG) is given sc, which suggests that AII may play an important role in mediating thirst during hypovolemia. However, the 3 present studies show that male albino Sprague-Dawley rats (N?=?57) with SFO lesions drank normal amounts when larger plasma volume deficits were caused by 30% PEG treatment. Ss did not drink in response to relatively low doses of hypertonic saline but drank normal amounts when given larger doses. Results suggest that the SFO is involved in a control system for thirst and that after damage to it, greater stimulation than usual may be required for drinking to be initiated. From this perspective, drinking would be expected following either suprathreshold stimulation or drug-induced lowering of the activation threshold in these animals, as was observed, with the loss of putative AII receptors in the SFO also contributing to their particularly severe deficits in thirst induced by AII. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ingestive responses to homeostatic challenges in rats with ablations of the anterolateral neocortex.

Because rats with either anterolateral neocortical (AN) or lateral hypothalamic (LH) damage initially display similar feeding and drinking deficits and recovery patterns, the present study examined the possibility that anterolateral neocortical ablations would also produce similar chronic ingestive impairments to glucoprivic and hydrational challenges. 73 male Sprague-Dawley rats received AN or dorsoposterior neocortical lesions or served as unoperated controls. Ss with AN ablations exhibited normal feeding responses to food deprivation and glucoprivation induced by insulin (4–26 U/kg, sc) or 2-deoxydextroglucose (2-DG [125 or 250 mg/kg, ip]), but their response to 500 mg/kg or 2-DG was impaired. These Ss also drank normally in response to hypertonic saline injections and following water deprivation but only if food was available during the test session. Results indicate that, although the anterolateral neocortex and LH are anatomically related, these brain regions appear to be functionally dissimilar in terms of the regulation of ingestion. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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-converting enzyme in subfornical organ mediates captopril-induced drinking.

These experiments tested whether angiotensin-converting enzyme (ACE) located within the subfornical organ (SFO) participates in the generation of water intake during peripheral ACE blockade with captopril (CAP). Lesions of the SFO virtually abolished drinking in response to intraperitoneal CAP injection. Intracranially injected CAP suppressed drinking induced by intraperitoneal CAP more completely with direct SFO injection compared with intraventricular or control tissue injections. This central captopril treatment did not alter the drinking response to subcutaneous hypertonic saline. Intraventricular injections of the angiotensin II (ANG II) receptor blocker sarile reduced drinking during oral captopril treatment in rats rehydrating from water deprivation. The results indicate that (a) the SFO mediates drinking caused by peripheral ACE inhibition; (b) the ACE located within the SFO may locally convert ANG I to ANG II, which then stimulates thirst; and (c) central ANG II receptors mediate thirst caused by peripheral ACE inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoptic angiotensin and salt appetite.

Two experiments were designed to test whether angiotensin (ANG) synthesis or receptor activation in the ventral preoptic region is critical for ANG-induced salt appetite in rats. In Experiment 1, infusions of ANG into the subfornical organ (SFO) produced water drinking without saline intake, but infusions near the organum vasculosum laminae terminals (OVLT) produced both water and saline drinking. Thus, forebrain areas that support water drinking to ANG do not all support salt appetite. In Experiment 2, rats were given oral captopril (CAP) to enhance daily intake of water and saline solution by increasing ANG II synthesis in the brain. CAP microinjected into the SFO reduced CAP-enhanced water drinking without affecting saline intake, but CAP in the OVLT reduced enhanced saline intake without affecting water drinking. Thus, ANG acting in the OVLT, the most ventral part of the median preoptic nucleus, or other nearby structures is important for ANG-induced saline appetite. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forebrain lesions differentially affect drinking elicited by dipsogenic challenges and injections of muscimol into the median raphe nucleus.

Injections of muscimol into the median raphe nucleus (MR) elicit intense drinking in normally hydrated rats. To determine whether this response is dependent on forebrain systems mediating other aspects of water intake, the authors examined the effects of lesions of the subfornical organ (SFO), median preoptic nucleus (MnPO), lateral preoptic area (LPO), or lateral hypothalamus (LH) on the drinking. Lesions of the SFO or LH attenuated muscimol-elicited drinking, whereas lesions of the MnPO or LPO increased water intake after the treatment. All of the lesion groups showed a deficit in drinking to injections of polyethylene glycol and at least one of the doses of hypertonic saline. Only the SFO- and LH-lesioned groups showed a suppression of drinking to systemic injections of angiotensin II, suggesting that the drinking elicited by intra-MR injections of muscimol may involve changes in the central circuits mediating angiotensin-induced drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subfornical organ participates in salt appetite.

The effects of subfornical organ (SFO) lesions on salt and water intakes after sodium depletion were studied. Water and salt intakes were measured over 45 hr during a regimen that combined furosemide diuresis and access to low-sodium diet. Water was solely available for 23 hr after diuresis, and water and 0.3 M NaCl solution were available in choice for the next 22 hr. After diuresis, rats with SFO lesions drank significantly less water in 2 hr than controls but achieved equivalent water and sodium balances before salt access 20 hr later. After salt access, rats with SFO lesions drank significantly less saline and water in 2 hr than controls but had similar saline and water intakes over the next 20 hr. Thus, SFO lesions blunted acutely, but not chronically, saline and water intakes to sodium depletion, and the blunted intakes are not explainable by hydrational status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenocortical response to hypertonic saline in rats with lateral hypothalamic lesions.

Used plasma corticosterone levels to assess the response to stress induced by ip injections of hypertonic saline in 27 male albino Harlan-Sprague rats with lateral hypothalamic (LH) or sham lesions. Ss with LH lesions displayed a corticosterone response equal to that of normal Ss under basal conditions, after control injections of isotonic saline, and 20 min after injection of hypertonic saline (1.5 M, 1.0 ml/100 g of body weight). The corticosterone response of Ss with LH lesions, however, was significantly less than that of normal Ss 90 min after injection of hypertonic saline when no water was available. With access to water, normal Ss displayed substantial drinking (14.5 ml/90 min), which resulted in a reduction in plasma corticosterone concentrations to a level observed after a control injection of isotonic saline, but the little water ingested by Ss with LH lesions (2.5 ml) had no effect on the pituitary-adrenal system. It is concluded that the failure of Ss with LH lesions to drink following a hydrational challenge is not the result of an exaggerated response to stress. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A vagally mediated histaminergic component of food-related drinking in the rat.

Six experiments with 95 male albino Sprague-Dawley rats (1) demonstrated that exogenous histamine was a potent stimulus for drinking behavior that was dependent upon an intact abdominal vagus and (2) provided evidence for a histaminergic component of the stimulus for food-related drinking in the rat. Histamine elicited drinking in a dose-related manner typically within 5 min after sc injection in Ss. Threshold for increased drinking was 1.25 mg/kg, and 2.5 mg/kg elicited half of the maximal drinking response that followed 20 mg/kg. Bilateral subdiaphragmatic vagotomy, with the hepatic branch left intact, severely attenuated drinking in response to systemic histamine: Vagotomized Ss drank later and less than did normal Ss after doses of histamine between 1.25 and 40 mg/kg. This attenuation was attributed to the destruction of vagal afferent fibers because histamine-elicited drinking was not affected by blockade of vagal efferents with atropine methyl nitrate. Drugs antagonistic to peripheral H? histamine receptors specifically inhibited drinking in response to histamine: Cimetidine or metiamide injected ip delayed and decreased drinking after sc histamine and temporarily decreased drinking after hypovolemia produced by sc polyethylene glycol, but failed to inhibit drinking after water deprivation, cellular dehydration, or isoproterenol. Finally, cimetidine or metiamide inhibited drinking in temporal association with a meal of liquid or solid food without slowing the rate of eating or decreasing food intake. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Septal hyperdipsia: Specific enhancement of drinking to angiotensin in rats.

Conducted 3 experiments with a total of 126 hyperdipsic and 123 normal female Sprague-Dawley rats. Ss made hyperdipsic by destruction of the septal nuclei drank more water than normal Ss to thirst stimuli considered to be mediated, at least in part, by angiotensin. Specifically, they drank more than normal Ss to caval ligation, hypotension induced by the b-adrenergic agonist isoproterenol, intraperitoneal injections of renin, and intravenous infusions of angiotensin. Overdrinking was enhanced by nephrectomy when renin or angiotensin were introduced exogenously, but nephrectomy reduced drinking to hypotension. Septal hyperdipsic Ss drank more water than normal Ss when polyethylene glycol was delivered intraperitoneally but not subcutaneously. They did not drink more to cellular dehydration produced by the intravenous or intragastric injection of hypertonic saline or sucrose. The contributions of the septum to angiotensin-mediated drinking and to nonhomeostatic determinants of drinking are discussed, as are the possible mechanisms controlling drinking to intravascular depletions. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bradykinin suppresses alcohol intake and plays a role in the suppression produced by an ACE inhibitor

The possible role of the endogenous kinins in the control of alcohol intake was assessed in two experiments. In Experiment 1, naive rats, maintained on ad lib food and water, were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal (IP) injections of captopril (20 mg/kg) significantly reduced alcohol intake, while pretreatment with subcutaneous (SC) injections of the bradykinin antagonist [D-Phe7]-bradykinin (100-300 micrograms/kg) attenuated the suppressive effect of captopril on alcohol intake. The saline vehicle or the bradykinin antagonist alone did not alter alcohol intake. In Experiment 2, bradykinin was administered daily at 100, 200, and 400 micrograms/kg doses SC either alone or in combination with captopril 10 mg/kg IP. Neither bradykinin nor captopril by themselves changed alcohol or water intake. Bradykinin combined with captopril stimulated water intake and reduced alcohol intake by up to 70%. This effect was not due to drug-induced changes in the pharmacokinetics of alcohol. The angiotensin II receptor antagonist [Sar1,Thr8]-angiotensin II at 250 and 500 micrograms/kg SC attenuated the stimulation of water intake but not the reduction in alcohol intake. It is suggested that by inhibiting kininase II, ACE inhibitors extend the duration of action of bradykinin and thereby unmask a potent inhibition of alcohol intake mediated by kinins--an effect that is dissociable from the accompanying stimulation of water intake. Taken together, these results point to an involvement of the kinin system in the regulation of alcohol intake and in particular to a role of bradykinin in the suppressive effect of ACE inhibitors on alcohol intake.     

Role of anorexia and behavioral activation in amphetamine-induced suppression of feeding: Implications for understanding tolerance.

48 male Sprague-Dawley albino rats administered chronic injections of either saline or dextroamphetamine (DAM) sulfate (2 or 4 mg/kg, intraperitoneally) were given milk either directly into the mouth through an intraoral cannula or in a standard drinking tube. Results reveal that bottle-fed Ss given DAM showed substantially greater suppression of intake than cannula-fed Ss. Saline-treated Ss showed almost identical milk intake with the 2 methods. Recovery of intake occurred in all drugged Ss except those given 4 mg/kg and fed by bottle. In the tolerant groups, Ss fed by bottle and given 2 mg/kg recovered at a faster rate than cannula-fed Ss at either dose. Findings demonstrate that in a normal drinking condition, the initial suppression of intake is caused by a combination of anorexia and behavioral interference and that tolerance occurs to both of these effects. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of an ascending dose regimen on the development of tolerance to the anticonvulsant effect of diazepam.

Assessed the effect of an ascending dose regimen on the development of tolerance to diazepam's anticonvulsant effect. During the 22 trials of the tolerance development phase, 55 adult male, amygdala-kindled rats received either a series of dosage injections ranging from high (10 mg/kg), to low (1 mg/kg), and ascending (1 mg/kg and increased by 0.2-mg/kg increments to 3 mg/kg) or saline injections. Diazepam was administered by intraperitoneal/ly (ip) injection once every 48 hrs, and each injection was followed 1 hr later by a convulsive stimulation. The ascending dose rats displayed significantly more tolerance to the anticonvulsant effect of diazepam than did the high dose, low dose, or saline rats. By contrast, both the ascending and high dose rats displayed a significant withdrawal effect (i.e., increased duration of convulsions) after the cessation of diazepam injections. Results demonstrate that administration of ascending dosages can facilitate the development of tolerance to anticonvulsant drug effects and that tolerance and withdrawal are not necessarily inextricably related. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abdominal vagotomy inhibits osmotically induced drinking in the rat.

Results of a study with 35 male Sprague-Dawley rats show that after complete bilateral transection of the abdominal vagus (Vgx-C9), with the hepatic branch left intact, Ss drank later and less than normal after cellular dehydration induced by hypertonic saline. When access to water was delayed for 1 hr after cellular dehydration, Vgx-C Ss initiated drinking quickly with normal latency, but (a) a gastric water preload was a more effective stimulus for drinking suppression in Vgx-C than in normal Ss; (b) gastric emptying of a water or phenol red solution preload was more rapid in Vgx-C than in normal Ss; and (c) when gastric emptying dysfunction in Vgx-C Ss was removed by having Ss sham drink, Vgx-C and normal Ss sham drank equivalent amounts of water. Thus, disordered preabsorptive satiety caused by abnormally rapid gastric emptying of water was a factor in the decreased drinking of Vgx-C rats after cellular dehydration. Disordered satiety for ingested water could not, however, account for the abnormal latency to initiate drinking after cellular dehydration in Vgx-C rats. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions of amygdala lesions with effects of pilocarpine and d-amphetamine on mouse killing, feeding, and drinking in rats

Repeated injections of 7.5 mg/kg pilocarpine induced mouse killing in both amygdala-lesioned and sham-operated rats, but more injections were required in the lesioned animals. Killing was evoked least readily in rats that showed substantial weight loss after surgery and that had damage to more medial regions of the amygdala. d-Amphetamine (.75, 1.50, or 3.00 mg/kg), administered either before or after a killing test, inhibited pilocarpine-induced killing in both surgical groups. Amygdala lesions attenuated pilocarpine-facilitated drinking in sated animals but did not alter the inhibitory effects of either pilocarpine or d-amphetamine on feeding or drinking.     

Osmoregulatory thirst in rats after lateral preoptic lesions.

Conducted 5 experiments using a variety of dehydrational procedures to characterize drinking behavior in rats with lesions of the lateral preoptic area (LPO). In confirmation of previous observations, lesions of the LPO in male albino Sprague-Dawley rats abolished water ingestion during a 4-hr test following an ip injection of hypertonic NaCl solution. These Ss increased their water intakes when tests were prolonged to 24 hrs and drank almost exactly what they needed for osmoregulation. Furthermore, they increased their water intakes normally when NaCl was given in their diet, when NaCl was administered iv, or when they were water deprived and given preloads of isotonic saline to remove hypovolemia. These findings indicate that rats with lateral preoptic lesions do experience osmoregulatory thirst, and raise new doubts about whether osmoreceptors located in the lateral preoptic area mediate thirst following the administration of osmotic loads. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Etiological role of cadmium in hypertension in an animal model

Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats were used to determine whether cadmium plays an etiological role in hypertension. In Study I, weanling (3-week-old) R and S rats of both sexes were given a low-salt (0.4% NaCl) diet and were divided into two groups. Rats in the cadmium group were injected with cadmium (2 mg/kg body weight, ip), whereas the controls received identical volumes of saline. Three weeks after the first injection, no elevations of systolic blood pressure were detected. A second dose of cadmium (1 mg/kg) produced hypertension in S females but not in S males or in R rats of either sex. Also, female S cadmium rats manifested significant (p less than 0.01) mild to moderate renal vascular changes. The concentrations of cadmium in hepatic and renal tissues of S cadmium rats were significantly higher (p less than 0.001) than in R rats. In Study II, weanling (3-week-old) female S rats on a high-salt (4% NaCl) diet were given cadmium (2 mg/kg body weight, ip) at week 3 followed by second and third injections of cadmium (1 mg/kg) at weeks 6 and 23. S controls received the same volumes of saline. Cadmium enhanced the rate and the degree of salt-induced hypertension development. Pathological lesions of periarteritis nodosa in the mesenteric arteries and renal vascular lesions occurred to the same extent in the cadmium and control groups. These data indicate that differences in genetic background influence the development of cadmium-induced hypertension in weanling rats, and that cadmium exacerbates the severity of salt-induced hypertension.     

Effect of serotonergic and catecholaminergic antagonists on mild-stress-induced excessive grooming in the rat.

Studied the action of the dopamine antagonist haloperidol, the serotonin antagonists methysergide and pizotifen (pizotyline), and the alpha- and beta-adrenoceptor antagonists phentolamine and levo-propranolol on the grooming response to a mild stress in male Holtzman rats. Excessive grooming induced by 2 ip injections of physiological saline did not modify open-field locomotion in 5-min trials. Methysergide (15 mg/kg, ip) and pizotyline (5 mg/kg, ip) selectively prevented the grooming response to saline without affecting locomotion. Haloperidol (.4 mg/kg) also prevented excessive grooming. However, it also impaired locomotion. Phentolamine (20 mg/kg) and levo-propranolol (20 mg/kg) did not prevent the excessive grooming in response to saline and did not affect locomotion. Results suggest that some serotonergic pathways in the brain are involved in the grooming response to a mild stress and support previous findings on the role of dopaminergic systems on this activity. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)