Significant Increase In Water Intake Research Articles

The relationship between ghrelin and inflammation in diabetic rat stomach

Ghrelin is a hormone that regulates the digestive system, as well as has immunomodulating effects. The aim of this study is to explain effects of ghrelin on inflammation and oxidative stress parameters in the stomach. Male Sprague Dawley rats 8-10 weeks old (n = 21) were randomly divided into three groups as control, type 2 diabetes (T2DM) and diabetes and given exogenous ghrelin (T2DM+Gh). The daily feed and water intake of the animals were measured. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) mRNA in tissues were analyzed using RT-PCR technique. Ghrelin and nuclear factor-κβ (NF-κβ) peptides were detected by immunohistochemistry. T2DM group had a significant increase in water intake when compared to control group. T2DM group had significantly higher levels of IL-6, IL-1, and IL-10 mRNA expression than control group. IL-1β and IL-10 mRNA expression were significantly lower in T2DM+Gh group than in T2DM group. In T2DM group, NF-κβ was higher than in control group, but it was lower in T2DM+Gh group. In terms of oxidative stress, there were non-significant changes. According to our findings, exogenous ghrelin intake was found to be highly effective in reducing inflammation in stomach tissue with type 2 diabetes (Tab. 1, Fig. 3, Ref. 33). Text in PDF www.elis.sk Keywords: ghrelin, rat, type 2 diabetes, stomach, inflammation.

β-Lactamase inhibitor, clavulanic acid, attenuates ethanol intake and increases glial glutamate transporters expression in alcohol preferring rats.

Studies from our laboratory showed that upregulation of glutamate transporter 1 (GLT-1) and cystine-glutamate exchanger (xCT) expression with ceftriaxone, β-lactam antibiotic, in the brain was associated with attenuation of ethanol consumption. In this study, we tested clavulanic acid, which is another β-lactam compound with negligible antimicrobial activity, on ethanol consumption and expression of GLT-1, xCT and glutamate aspartate transporter (GLAST) in male alcohol-preferring (P) rats. Clavulanic acid has the central β-lactam pharmacophore that is critical for the upregulation of GLT-1 and xCT expression. We found that clavulanic acid, at 5mg/kg (i.p.) dose, significantly attenuated ethanol consumption and ethanol preference in P rats as compared to vehicle-treated group. This effect was associated with a significant increase in water intake in clavulanic acid treated group. Importantly, we found that clavulanic acid increased the expression of GLT-1 and xCT in nucleus accumbens. However, there was no effect of clavulanic acid on GLAST expression in the nucleus accumbens. Clavulanic acid treatment did not upregulate the expression of GLT-1, xCT and GLAST in prefrontal cortex. These findings revealed that clavulanic acid at 20-40 fold lower dose than ceftriaxone can attenuate ethanol consumption, in part through upregulation of GLT-1 and xCT expression in the nucleus accumbens. Thus, we suggest that clavulanic acid might be used as an alternative option to ceftriaxone to attenuate ethanol drinking behavior.

High Salt Diet Plus Fructose Water Intake Induces Hypertension

Evidence in prior studies have indicated that a high salt (HS) diet in combination with high fructose intake results in hypertension. Detailed metabolic parameters have not measured. This study aims to test the metabolism of rats with either a HS diet or a normal salt (NS) diet with and without fructose drinking water. Seven‐week‐old, Sprague‐Dawley (SD), male rats were divided into four groups (n=6 per group). The SD rats were then fed the following diets: NS diet as the control, HS (4% NaCl) diet, NS diet with 20% fructose in drinking water (F), and HS (4% NaCl) diet with 20% fructose in drinking water (HS+F), respectively. Blood pressures of all the rats were then measured twice a week via non‐invasive tail cuff method. Two weeks after the blood pressure measurements, all the rats were then transferred into metabolic cages and housed individually. In the metabolic cages, the rats received the same diet and drinking water as they have had throughout the entire blood pressure study. SD rats were given twenty‐four hours to acclimate to their environment in the metabolic cages and then their water intake, food intake, feces and urine output was measured for three consecutive days. At the beginning of the experiment, results have indicated that there is no significant difference in baseline blood pressure among the four groups. However, A three‐week diet of a HS+F treatment has demonstrated an increase in mean arterial pressure (MAP) by 37 mmHg (p < 0.05) compared to the NS control group. No significant increases were observed in the other two groups (C: 89 ± 5; HS: 97 ± 4; F: 97± 7; HS+F: 126 ± 9 mmHg). Metabolic measurements have shown that there was a significant increase in water intake (C: 27.9 ± 2.0; HS: 59.2 ± 6.4; F: 35.1 ± 5.2; HS+F: 54.8 ± 6.0, mL/24 hours) and urine output (C: 13.5 ± 1.7; HS: 39.7 ± 2.2; F: 13.3± 1.6; HS+F: 28.1 ± 1.4, mL/24 hours) for HS alone and HS+F groups in comparison to the control group. Food intake had substantially decreased in the HS+F group compared to the other three groups (P<0.05) (C: 36.1 ± 3.6, HS: 25.1± 0.9, F: 21.7 ± 0.7, HS+F: 14.5 ± 1.0, mL/24 hours); the feces output data was diverse and does not show significant differences among groups (data not shown). Our results suggest that high salt plus high fructose diet dramatically changes metabolism which alters cardiovascular function.Support or Funding InformationGrant Support: NIH R15HL129213, Shan

D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats

The present study was aimed to assess the antihyperlipidemic, antihypertensive and antioxidant effect of D-carvone, a monoterpene against Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension. Hypertension was prompted in adult male albino rats of the Wistar strain by oral administration of the L-NAME (40 mg/kg body weight) in drinking water for 4 weeks. Rats were treated with D-carvone (5, 10 and 20 mg/kg body weight) for four weeks. L-NAME treated rats exhibited significant increase in water intake, heart rate, aortic lipids level such as triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and significant decrease in the level of phospholipids (PL), plasma nitric oxide (NO). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were decreased in erythrocytes of L-NAME induced hypertensive rats. Treatment with D-carvone restored all the above parameters to near normal level. These results suggest that D-carvone acts as an antihyperlipidemic, antihypertensive and antioxidant agent against L-NAME induced hypertensive rats.

D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats

The present study was aimed to assess the antihyperlipidemic, antihypertensive and antioxidant effect of D-carvone, a monoterpene against Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension. Hypertension was prompted in adult male albino rats of the Wistar strain by oral administration of the L-NAME (40 mg/kg body weight) in drinking water for 4 weeks. Rats were treated with D-carvone (5, 10 and 20 mg/kg body weight) for four weeks. L-NAME treated rats exhibited significant increase in water intake, heart rate, aortic lipids level such as triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and significant decrease in the level of phospholipids (PL), plasma nitric oxide (NO). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were decreased in erythrocytes of L-NAME induced hypertensive rats. Treatment with D-carvone restored all the above parameters to near normal level. These results suggest that D-carvone acts as an antihyperlipidemic, antihypertensive and antioxidant agent against L-NAME induced hypertensive rats.

Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?

Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986-1998, 853 patients); Group 2, narrow-band era (1999-2004, 467 patients); Group 3, broad-band era (2005-2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend<0.001) and a decrease in urinary sodium and chloride for both genders and calcium and magnesium only for males, while females experienced a slight increase in oxalate excretion. Supersaturation indexes for calcium and uric acid stones dramatically fell for both genders. The percentage of stone formers performing physical activity significantly rise (41% Group 3 vs. 8% Group 1, p<0.001) and we also found a trend of reduction in mean blood pressure. Therefore, the lifestyle of Italian idiopathic calcium stone formers has changed over the last 25 years, and the rising Internet access may have played a great role in driving this change.

Abstract 394: Chronic Knockdown of the NTS AT1R Increases Circulating Inflammatory-Endothelial Progenitor Cells Ratio and Exacerbates Hypertension in the SHR

AT1R expression is increased in the nucleus of solitary tract (NTS) of many animal models of hypertension. However, the impact of its chronic regulation on cardiovascular control is not well understood. In this study, we investigated the hypothesis that NTS AT1R is involved in peripheral inflammatory status and hypertension-linked cardiovascular pathophysiology. AAV2- mediated expression of a shRNA targeted the AT1R in the NTS has been used to test the hypothesis. First,the efficacy of the AAV2-AR1R-shRNA was established with the use of neuronal cells in primary culture. Transduction of these cultures by AAV2-AT1R-shRNA resulted in a 72% decrease in AT1R mRNA compared with the AAV2- Sc-shRNA transduced control. This was accompanied by complete attenuation of AngII-induced increase in ERK1/2 phosphorylation and neuronal action potential frequency (control: 2.2±0.4 vs. AT1R-shRNA: 0.5±0.3 hz). We then microinjected AAV2-AT1R-shRNA or control vector, AAV2-Scrambled (Sc)-shRNA into the NTS of 8-week-old SHR and WKY rats. Nine weeks following microinjection, AAV2-AT1R-shRNA group of SHRs showed a 29 mmHg increase in mean arterial pressure (MAP) (control: 154.2±4.7; shRNA: 183.0±10.2 mmHg), insignificant effects on the MAP of WKY rats was observed. The increase in MAP in the SHR by AAV2-AT1R-shRNA was associated with a 42% decrease in baroreflex bradycardia (control: 0.57±0.02; shRNA: 0.33±0.06 ms/mmHg), profound cardiac hypertrophy, and significant increase in the plasma norepinephrine (control: 6.36±0.39, shRNA: 13.0±4.13 ng/mL). In addition, AAV2-AT1R-shRNA rats showed significant increases in water intake (control: 32.5±1.5; shRNA: 12.5±2.5 ml/16h) and urine output (control: 1.6 ±0.5; shRNA: 9.3±2.5 ml/16h). Furthermore, AAV2-AT1R-shRNA treated SHR exhibited 74% decrease in circulating endothelial progenitor cells (EPC, CD90+, CD4/5/8-), and ∼300% increases in inflammatory cells (IC) including CD4/8+, T lymphocytes (CD45/3+) and macrophages (CD68+) . As a result, EPC/IC ratio was decreased by 8∼15 fold in AT1R-shRNA treated SHR. These observations suggest that increased AT1R in the NTS of SHR may present a counter-hypertensive mechanism involving inflammatory/angiogenic cells.

Relationship of Early Lactation and Bovine Somatotropin to Water Metabolism and Mammary Circulation of Crossbred Holstein Cattle

The study was carried out to evaluate the effect of exogenous bovine somatotropin on water metabolism in relation to mammary function in early lactation of crossbred Holstein cattle. Ten, 87.5% crossbred Holstein cattle were divided into two groups of 5 animals each. At day 60 of lactation, the control group was given placebo while animals in the experimental group were given recombinant bovine somatotropin (rbST) by subcutaneous injection with 500 mg of rbST (14-days prolonged-release rbST). In rbST- treated animals, milk yield increased 19.8%, which coincided with a significant increase in water intake (p<0.01), while DM daily intake was not different when compared to the control animals. Water turnover rate as absolute values significantly increased (p<0.05), while the biological half-life of water did not change in rbST-treated animals. Total body water (TBW) and total body water space (TOH) as absolute values significantly increased (p<0.01) in rbST-treated animals, while it was decreased in the control animals. Absolute values of empty body water (EBW) markedly increased (p<0.05), which was associated with an increase in the extracellular fluid (ECF) volume. Absolute values of plasma volume and blood volume were also significantly increased (p<0.05) in rbST-treated animals. The increase in mammary blood flow in rbST-treated animals was proportionally higher than an increase in milk production. The plasma IGF-1 concentration was significantly increased (p<0.01) in rbST-treated animals when compared with those of control animals during the treatment period. Milk fat concentration increased during rbST treatment, while the concentrations of both protein and lactose in milk were not affected. The present results indicate that rbST exerts its effect on an increase in both TBW and EBW. An increased ECF compartment in rbST-treated animals might partly result from the decrease in fat mass during early lactation. The action of rbST on mammary blood flow might not be mediated solely by the action of IGF-1 for increase in blood flow to mammary gland. An elevation of body fluid during rbST treatment in early lactation may be partly a result of an increase in mammary blood flow in distribution of milk precursors to the gland. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 11 : 1600-1608)

Tolerance of imported rabbits grown as meat animals to hot climate and saline drinking water in the subtropical environment of Egypt

AbstractNinety of each of New Zealand White (NZW) and Californian (Cal) male weaned rabbits at 5 weeks of age with nearly similar average live weights were used during two periods of the year (mild and hot, each of 9 weeks), in a trial to evaluate their adaptability as meat animals to the subtropical conditions of Egypt. The results showed that NZW surpassed Cal, in most of the traits studied. The increase was significant in final live weight, daily weight gain, final body solids, daily body solids gain, body water concentration (ml per 100 g body solids) and pre-slaughter weight. Meanwhile, Cal significantly surpassed NZW in daily water consumption. The temperature-humidity index (THI) values indicated absence of heat stress in the first period and exposure to moderate (but very close to severe) heat stress in the second. The hot conditions induced significant decline in final live weight, daily weight gain, food intake, final body solids, daily body solids gain, plasma tri-iodothyronine (T3) hormone, total proteins, albumin, globulin, total lipids, glucose, electrolytes (Na, K, Ca, Mg and P), pre-slaughter weight and kidneys with fat weight. In contrast, the hot conditions were accompanied by significant increases in water intake, body water concentration, plasma urea-N, creatinine and physiological body reactions (respiration rate and temperatures of rectum, skin and ear). Drinking water containing high levels of salt (3000 p. p. m. and more) caused significant decreases in final live weight, daily live-weight gain, final body solids, daily body solids gain, plasma T3 hormone, total proteins, albumin, total lipids, glucose, pre-slaughter weight and kidneys with fat weight. At the same time, significant increases occurred in water consumption, body water concentration, plasma urea-N, creatinine, electrolytes (Na, K, Ca and P), respiration rate and rectal and skin temperatures. Estimations of adaptability to the subtropical environment of Egypt and tolerance to drinking saline water under the same conditions were found to be proportionately 0·844 and 0·876 and 0·821 and 0·803, in NZW and Cal, respectively.

Effects of Topiramate on Ethanol and Saccharin Consumption and Preferences in C57BL/6J Mice

Topiramate has recently been found to be more effective than placebo as an adjunct treatment for alcohol dependence, but it has not yet been investigated in animal models of ethanol consumption. The current experiment examined the effects of topiramate on ethanol drinking in mice using a continuous access, two-bottle choice procedure. C57BL/6J male mice were offered a 10% v/v ethanol solution versus tap water over 4 consecutive days per week. Mice were assigned to topiramate (1-50 mg/kg) or saline groups and received injections before the beginning of the dark phase of the light cycle. Topiramate dose increased over 5 successive weeks (1, 5, 10, 25, and 50 mg/kg). Fluid intake was measured 2, 4, and 23 hr after injection. Body weight and food intake were measured at the time of injection. In a second phase, mice were offered saccharin solutions (0.2 and 2.5% w/v) versus tap water after topiramate (50 mg/kg) or saline injections. Results revealed that high topiramate doses (25 and 50 mg/kg) increased water intake and decreased ethanol preference. Compared with saline controls, topiramate produced dose-dependent, bidirectional effects on ethanol dose, with 25 mg/kg of topiramate increasing ethanol dose at 4 and 23 hr after injection but 50 mg/kg topiramate decreasing ethanol dose at 2 hr after injection. During saccharin exposure, topiramate decreased saccharin preference (for 2.5% w/v saccharin solution) and marginally increased water intake but did not directly alter intake of the saccharin solutions. Topiramate had no effects on body weight or daily food intakes. Topiramate reduced ethanol preference in C57BL/6J mice, but this effect was primarily attributable to elevated water intake. Topiramate also reduced saccharin preference, likely through marginally significant increases in water intake. Increases in water intake and bidirectional effects of topiramate on ethanol dose complicate conclusions with regard to the effects of topiramate on ethanol reward.

The effects of offering mineral blocks to ewes pre-mating and in late pregnancy on block intake, pregnant ewe performance and immunoglobulin status of the progeny

AbstractTwo experiments were carried out to quantify the intake of mineral blocks by ewes in group- and individually fed situations, and to examine the effects of mineral block intake on food and water intake, colostrum production and lambs' immunoglobulin G (IgG) absorption when ewes are individually housed and offered maize or grass silage with a concentrate supplement. In experiment 1, mineral blocks were offered to 359 ewes either when grazing at mating time (no. = 200) or, when indoors in the last 4 or 7 weeks of pregnancy, the latter as either twin-bearing ewes that were group-fed (no. = 18) or individually fed (no. = 27) or single-bearing ewes that were group-fed (no. = 114). Block intake was measured on a weekly basis. In experiment 2,a2X2 X 2 factorial design was used to compare the effects of forage (grass or maize silage), restricted mineral block access and added minerals/vitamins in the concentrate on food and water intakes, colostrum production and immunoglobulin absorption by the lamb using 64 twin- bearing ewes that were individually housed. Grass silage and maize silage were offered ad libitum, concentrates were offered at a flat rate of 400 g per head per day. Mineral blocks were offered to ewes for 3 h/day. Following lambing, the ewes were hand milked at 1,10 and 18 h post partum. Colostrum samples were assayed for immunoglobulin G (IgG) content. Lambs were blood sampled at 24 h old to determine serum IgG value. In experiment 1, mean daily mineral block intake per ewe was lowest at mating time (19 g) and highest when ewes were individually housed (194 g). In experiment 2, intakes of dry matter(DM) and energy were higher (F &lt; 0.05) in the maize silage treatments. Similarly, when ewes had access to mineral blocks they had higher (P &lt; 0.05) intakes of DM, energy and protein in addition to having a higher water intake (2.24 v. 0.771 per ewe per day; s.e. 0.139; P &lt; 0.01). The mean total colostrum yield to 18 h post lambing at 1734 ±98.0 ml was unaffected by any of the treatments. When ewes had access to mineral blocks their lambs had lower (6.8 v. 18.8; s.e. 1.48; P &lt; 0.01) serum IgG values and the efficiency of IgG absorption from the colostrum into the blood stream was reduced (0.097 v. 0.247; s.e. 0.0214; P &lt; 0.01). In conclusion, the data show that there is wide variation in mineral block intake in different situations and that intake of some minerals can exceed toxic values. Additionally, when individually fed pregnant ewes have access to blocks for just 3 h/day, there is a significant increase in water intake and a dramatic reduction in lamb serum IgG concentration and in the efficiency of absorption of colostral IgG into the blood. We suggest that while mineral blocks can confer advantages in specific situations, there is the need to revisit their formulation and to further research the mode of action responsible for the compromised IgG absorption.

Quantitative histochemical assessment of oxidative metabolism in the subfornical organ after partial aortic ligature in rats

Circumventricular organs are considered to be involved in hydromineral homeostatic responses. In this study we used quantitative histochemistry of cytochrome oxidase to evaluate the oxidative metabolic activity of the subfornical organ of rats with a partial aortic occlusion. These rats showed a significant increase in water intake from the second day after the ligature, while natriophilia was already significant on the first day. Greater levels of cytochrome oxidase activity were found in subfornical organs of partial aortic ligated rats when compared with control, providing further evidence for the involvement of this circumventricular structure in fluid homeostasis at least in this hyperdipsic, hypernatriophilic, hyperreninemic and hypertensive experimental model.

Partial aortic ligature induces selective long-term c-fos like immunoreactivity in the organum vasculosum of the lamina terminalis, medial preoptic area and choroid plexus in the rat

Partial aortic ligature causes an increase in water and sodium intake. Circumventricular brain regions are known to be involved in the regulation of these processes. In this work we use c-fos-like immunoreactivity to detect active areas involved in the long-term control of increased water and sodium intake due to partial aortic ligature. A significant increase in water intake was found on the first day after the induction, while natriophilia was observed on the fourth day. c-fos-like immunoreactivity was found selectively in the subfornical organ, the organum vasculosum of the lamina terminalis, the medial preoptic area, and the choroid plexus of the third ventricle. Present results provide further evidence for the involvement of circumventricular organs and the preoptic area in the regulation of hydromineral balance. Moreover, they suggest a maintained and long-term regulation of sodium intake by these same brain areas.

Reduced food consumption increases water intake and modulates renal Aquaporin-1 and-2 expression in autoimmune prone mice

Aquaporin-1(AQP1) and AQP2 are members of the aquaporin family of cell membrane water channel transport proteins and have been implicated in the regulation of renal water excretion. We have previously shown that calorie restriction (CR) relative to ad libitum (AL) feeding extends lifespan and delays the onset of autoimmune kidney disease in lupus-prone (NZBxNZW)F1 (B/W) mice. To determine if AQP1 and/or AQP2 expression is influenced by CR, mice were fed an AL or CR (40% less food) diet until 4 (young) or 9 (old) months of age when mice were sacrificed. Kidneys were removed and the expression of AQP1 and AQP2 was determined at the protein and mRNA levels using western blotting and RT-PCR respectively. While age did not significantly increase AQP1 expression in the AL groups, CR did increase both the protein (1.4-fold) and mRNA (2.4-fold) levels. In old mice, AQP1 expression was higher (1.8-fold) in CR compared to the AL group while CR had no effect in young mice. In contrast, AQP2 showed an age related decrease (55%) in the AL groups and an increase in the protein (8.4-fold) and mRNA (1.7-fold) levels in the CR groups. Relative to AL, CR decreased AQP2 expression at the protein (90%) and mRNA (50%) levels in the young mice while an increase at the protein (2.9-fold) and mRNA (1.9-fold) levels was evident in the old mice. Interestingly, a significant increase in water intake per gram body weight was found in both young and old CR fed mice when compared to their AL counterparts which may contribute to the prevention of autoimmune disease with age and differences in longevity. These data show, for the first time, significant age and diet influences in renal AQP1 and AQP2 expression at both protein and mRNA levels in lupus-prone mice.

Zinc and water intake in rats: investigation of adrenergic and opiatergic central mechanisms.

We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ss-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 +/- 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 +/- 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 +/- 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 +/- 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 +/- 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 +/- 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ss-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides.

Chronic central infusion of ANG II potentiates cardiac sympathetic afferent reflex in dogs.

The aims of this study were to determine whether ANG II is involved in the central integration of the cardiac sympathetic afferent reflex (CSAR), and if this central effect of ANG II is mediated by the AT(1) receptor. Experiments were undertaken in dogs that were anesthetized with alpha-chloralose, sinoaortic denervated, and vagotomized. The renal sympathetic nerve activity (RSNA) responses to varying frequency and voltage stimulation of cardiac sympathetic afferent nerves were used to evaluate the central sensitivity of the CSAR. In two groups of dogs, two doses (50 and 100 ng/min icv) of ANG II were acutely infused. In a third group of dogs, ANG II was chronically infused for 3 days (100 ng/min, 1 microliter/h icv). We found that acute infusion into the cerebroventricle of two doses of ANG II did not affect the central sensitivity of the CSAR or the baseline hemodynamics, but the baseline RSNA increased significantly during the infusion of the higher dose of ANG II. However, chronic intracerebroventricular infusion of ANG II enhanced the central sensitivity of the CSAR significantly. In addition, chronic intracerebrovetricular infusion of ANG II elicited a significant increase in water intake and in arterial pressure from the first and second day of infusion, respectively. In the group that received chronic intracerebroventricular infusion of ANG II, the administration of an AT(1)-receptor antagonist losartan (0.125 mg/kg icv) abolished ANG II-induced augmentation of the CSAR. These results suggest that chronic elevation of central ANG II can sensitize the CSAR via central AT(1) receptors.

The role of glutamate transporter in neurological diseases

Studies from our laboratory showed that upregulation of glutamate transporter 1 (GLT-1) and cystine-glutamate exchanger (xCT) expression with ceftriaxone, β-lactam antibiotic, in the brain was associated with attenuation of ethanol consumption. In this study, we tested clavulanic acid, which is another β-lactam compound with negligible antimicrobial activity, on ethanol consumption and expression of GLT-1, xCT and glutamate aspartate transporter (GLAST) in male alcohol-preferring (P) rats. Clavulanic acid has the central β-lactam pharmacophore that is critical for the upregulation of GLT-1 and xCT expression. We found that clavulanic acid, at 5 mg/kg (i.p.) dose, significantly attenuated ethanol consumption and ethanol preference in P rats as compared to vehicle-treated group. This effect was associated with a significant increase in water intake in clavulanic acid treated group. Importantly, we found that clavulanic acid increased the expression of GLT-1 and xCT in nucleus accumbens. However, there was no effect of clavulanic acid on GLAST expression in the nucleus accumbens. Clavulanic acid treatment did not upregulate the expression of GLT-1, xCT and GLAST in prefrontal cortex. These findings revealed that clavulanic acid at 20–40 fold lower dose than ceftriaxone can attenuate ethanol consumption, in part through upregulation of GLT-1 and xCT expression in the nucleus accumbens. Thus, we suggest that clavulanic acid might be used as an alternative option to ceftriaxone to attenuate ethanol drinking behavior.

Pathophysiological role of glial glutamate transporters

Studies from our laboratory showed that upregulation of glutamate transporter 1 (GLT-1) and cystine-glutamate exchanger (xCT) expression with ceftriaxone, β-lactam antibiotic, in the brain was associated with attenuation of ethanol consumption. In this study, we tested clavulanic acid, which is another β-lactam compound with negligible antimicrobial activity, on ethanol consumption and expression of GLT-1, xCT and glutamate aspartate transporter (GLAST) in male alcohol-preferring (P) rats. Clavulanic acid has the central β-lactam pharmacophore that is critical for the upregulation of GLT-1 and xCT expression. We found that clavulanic acid, at 5 mg/kg (i.p.) dose, significantly attenuated ethanol consumption and ethanol preference in P rats as compared to vehicle-treated group. This effect was associated with a significant increase in water intake in clavulanic acid treated group. Importantly, we found that clavulanic acid increased the expression of GLT-1 and xCT in nucleus accumbens. However, there was no effect of clavulanic acid on GLAST expression in the nucleus accumbens. Clavulanic acid treatment did not upregulate the expression of GLT-1, xCT and GLAST in prefrontal cortex. These findings revealed that clavulanic acid at 20–40 fold lower dose than ceftriaxone can attenuate ethanol consumption, in part through upregulation of GLT-1 and xCT expression in the nucleus accumbens. Thus, we suggest that clavulanic acid might be used as an alternative option to ceftriaxone to attenuate ethanol drinking behavior.

Thermal dehydration-induced thirst in rats: role of body temperature.

Male Sprague-Dawley rats were used to study the possible role of hyperthermia in the thirst associated with thermal dehydration. Rats were exposed to 40 degrees C for 4 h and then allowed access to water at different times after they were transferred to 25 degrees C. Delaying the time prior to allowing the rats to drink did not significantly alter either water intake or percent rehydration even though core temperature decreased during the first 1.5 h after removal from the heat. Exposing thermally dehydrated rats to 5 degrees C for 30 min prior to allowing them access to water also failed to significantly affect water intake or percent rehydration. Thermally dehydrated rats allowed to drink while remaining in the heat did not show a significant increase in water intake during the first hour or percent rehydration over rats drinking at 25 degrees C. Nondehydrated rats did show significant increases in water intake and percent rehydration when allowed to drink in the heat. Hyperthermia does not play a role in drinking in thermally dehydrated rats but can stimulate drinking in water-replete rats.

Effects of ibotenic acid lesions of the ventral striatum and the medial prefrontal cortex on ethanol consumption in the rat

The purpose of this study was to to assess the effect on ethanol drinking of ibotenic acid lesions in the medial prefrontal cortex and the ventral striatum of female rats with continuous access to water and a 6% ethanol solution. Ibotenic acid infusions in the prefrontal cortex did not affect ethanol intake at any time, but a significant increase in water intake was observed on the third postoperative week. Ventral striatal lesions significantly increased ethanol intake during the first 2 postoperative weeks. On the third week consumption was not significantly different from vehicle-infused controls. Apparently, then, severe excitoxic injury to the ventral striatum is compatible with normal, or increased, intake of ethanol; in contrast, similar lesions reduce the intake of other drugs of abuse such as psychostimulants and opioids.