Decreased Water Intake Research Articles

Corticotrophin-releasing factor, vasopressin and pro-opiomelanocortin mRNA responses to stress and opiates in the rat.

1. Rats underwent either: (1) acute or chronic morphine or naloxone administration; (2) simple morphine withdrawal or naloxone-precipitated withdrawal in morphine-dependent animals; or (3) stress from I.P. administration of hypertonic saline. 2. Quantitative in situ hybridization histochemistry was performed using synthetic oligonucleotide probes for corticotrophin-releasing factor (CRF), vasopressin, pro-opiomelanocortin (POMC), dynorphin, enkephalin and oxytocin mRNAs. The paraventricular and supraoptic nuclei were examined in all studies and the arcuate nucleus and pituitary gland in the acute withdrawal study. 3. Neither acute nor chronic morphine administration altered either (a) hypothalamic parvocellular or magnocellular CRF mRNA, or (b) anterior pituitary or pars intermedia POMC mRNA. 4. Naloxone-precipitated morphine withdrawal resulted in a marked increase in parvocellular (but not magnocellular) CRF mRNA within 4 h and levels remained elevated through 24 h. There was no change in arcuate nucleus or pars intermedia POMC mRNA, but in the anterior pituitary there was a delayed increase, significant at 24 h. 5. Simple morphine withdrawal without the use of naloxone did not result in any change in CRF mRNA but there were increases in magnocellular vasopressin and dynorphin mRNA, presumably related to decreased water intake. 6. Intraperitoneal hypertonic saline stress also resulted in a marked accumulation of both parvocellular CRF and vasopressin mRNA without any concomitant change in magnocellular vasopressin mRNA. Increased translation of CRF mRNA was also evidenced by increased immunoreactive CRF detected by immunocytochemistry.

Apomorphine markedly potentiates naltrexone-induced hypodipsia in the rat

This article describes the effects of apomorphine on naltrexone-induced decreases in water intake of the rat deprived of water for 24 h. Apomorphine alone at reasonable doses (0.03, 0.1, 0.3 and 1.0 mg/kg) failed to affect water intake of the rat, but a higher dose (3.0 mg/kg) abolished water intake completely, accompanied by marked stereotypy. Naltrexone (0.1, 1.0 and 10.0 mg/kg) produced a dose-dependent reduction in water intake. A 0.3-mg/kg dose of apomorphine which is considered to activate preferentially presynaptic dopamine autoreceptors enhanced markedly naltrexone (1.0 and 10.0 mg/kg)-induced decreases in water intake. Only apomorphine at 1.0 mg/kg caused a significant prolongation of the latency to start drinking. Apomorphine (0.3 mg/kg), naltrexone (0.1, 1.0 and 10.0 mg/kg) or their combinations did not produce a marked effect on locomotor activity in the rat. These results suggest that apomorphine is capable of potentiating naltrexone-induced decreases in water intake through the mediation of presynaptic dopamine autoreceptors without causing motor dysfunction.

Effects of acute and chronic imipramine administration on conflict behavior in the rat: a potential "animal model" for the study of panic disorder?

Although numerous animal procedures have been employed in the study of generalized anxiety and agents effective in treating generalized anxiety, an analogous "behavioral model" for the study of panic disorder does not exist. In the present study, the effects of imipramine were examined in a potential "animal model" for panic disorder, the conditioned suppression of drinking (CSD) paradigm. In daily 10-min sessions, water-deprived rats were trained to drink from a tube that was occasionally electrified (0.5 mA). Electrification was signalled by a tone. Imipramine was administered both in an acute (3.5-20 mg/kg, IP) and a chronic (2.5 mg/kg, IP, twice daily for 5 weeks) regimen. Acute administration of imipramine resulted in a decrease in the number of shocks accepted and a decrease in water intake. In contrast, chronic administration of imipramine resulted in a gradual increase in the number of shocks received in CSD sessions over the course of several weeks of testing. This time-dependent increase in punished responding in the CSD observed during chronic imipramine treatment parallels the time-dependent reduction in the severity and frequency of panic attacks in panic disorder patients receiving chronic imipramine. Thus, the CSD paradigm might serve as an "animal model" for the study of panic disorder and potential anti-panic agents.

Kainic acid lesions of the nucleus accumbens selectively attenuate morphine self-administration

The influence of kainic acid lesions of intrinsic and efferent neurons of the central medial nucleus accumbens on responding simultaneously maintained by food, water and morphine self-administration was assessed. Rats were trained on a multioperant baseline to respond on three different levers that resulted in either a food pellet, the presentation of a water dipper or an infusion of morphine. While responding on the morphine lever was related to dose (0.83–13.2 mg/infusion), increasing concentrations of the drug had little or no effect on responding maintained by food and water before the lesion. Bilateral infusions of the neurotoxin into the nucleus accumbens decreased morphine self-administration but did not appreciably alter food or water intake. Food extinction probes before the lesion produced significant increases in drug intake and decreases in responding on the water lever, but the neurotoxin lesion attenuated the food extinction induced decrease in water intake. These data suggested that kainic acid lesions of the nucleus accumbens decrease the reinforcing efficacy of morphine but do not alter the reinforcing properties of food and water. The neuronal systems potentially involved in mediating the reinforcing effects of environmental events are discussed.

Toxicity of 2-hydrazinoethanol in turkey poults

1. 1. Toxicity of 2-hydrazinoethanol was investigated in turkey poults 2–6 weeks posthatch. 2. 2. Significant depression of body wt was evident at concentrations of the drug as low as 10 ppm. 3. 3. Severe anorexia closely paralleled a highly significant decrease in water intake. 4. 4. A significant increase in the ratio of granulocytes to agranulocytes was seen in poults fed the drug at a dose of 50 ppm. 5. 5. Under the conditions of this experiment, none of the tissues sampled exhibited pathologic changes consistent with drug injury.

A sex difference in the effect of CCK-8 on food and water intake in obese (ob/ob) and lean (+/+) mice

Male and female ob/ob and +/+ mice were tested with CCK-8 (1, 2, 4 and 8 μg/kg) administered 15 min prior to 30-min access to solid food after 17.5 hr food deprivation and 15 min prior to 30-min access to water after 17.5 hr water deprivation. The threshold dose for suppressing 30-min food intake was 2 μg/kg for all mice. Larger doses of CCK-8 inhibited food intake in male obese and lean mice in a linear fashion. The dose-response relationship for female mice, however, was not linear: lean females failed to suppress food intake following 4 or 8 μg/kg and obese females did not suppress food intake at 4 μg/kg. There was also a sex difference in the effect on water intake. No dose of CCK-8 changed water intake in lean males and only the 8 μg/kg dose decreased water intake in obese males. In contrast CCK-8 (1, 4 and 8 μg/kg) increased water intake in obese females, CCK-8 (1 and 8 μg/kg) increased water intake in lean females and no dose of CCK-8 decreased water intake in females. These data demonstrate significant sex differences in the effect of CCK-8 on food and water intake in mice.

Ritanserin and serotonergic mechanisms in blood pressure and fluid regulation in sheep.

1. In previous studies, exogenous serotonin (5-HT), administered intravenously, caused dose-related increases in mean arterial pressure and heart rate in conscious sheep. The 5-HT2 antagonist ketanserin (0.1 mg/kg per h, i.v.) was shown to lower blood pressure in the conscious sheep primarily through antagonism of alpha-adrenoceptors. 2. A newer 5-HT2 antagonist, ritanserin, is a more selective antagonist in vivo, as it attenuated or abolished pressor responses to exogenous 5-HT, but not to phenylephrine. 3. When infused alone, ritanserin (0.1 mg/kg per h, i.v.) failed to produce a decrease in blood pressure, suggesting that 5-HT antagonistic properties are not sufficient by themselves to lower blood pressure. 4. Ritanserin displayed a different metabolic profile to ketanserin, with a markedly decreased water intake. The mechanism of this effect is unresolved, but may imply a permissive role for 5-HT in the modulation of drinking responses in the sheep. 5. Ritanserin did not modify ACTH-induced hypertension in sheep.

Influence of tryptophan availability on selection of alcohol and water by men.

To study the effects of tryptophan on alcohol selection the tryptophan levels in subjects were altered through the administration of amino acid mixtures. Male social drinkers (N = 45) with no psychiatric or medical problems were divided into three groups and consumed a drink that contained, respectively, a nutritionally balanced amino acid mixture, a tryptophan-supplemented mixture, or a tryptophan-free mixture. After a waiting period of 5 hours, blood samples were taken and subjects participated in an ad-lib taste rating of six--one nonalcoholic and five alcoholic--beverages. Water was also made available to subjects. Although there was a marked effect on total and free plasma tryptophan levels showing a dramatic increase in the case of the tryptophan-supplemented group and a decrease in the tryptophan-free group, altered tryptophan levels did not influence the amount of alcohol subjects ingested. Tryptophan supplementation was found to decrease water intake significantly by an unknown mechanism without affecting alcohol selection.

Functional adaptation of thick ascending limb and internephron heterogeneity to urine concentration

The kidney is able to adapt to a variety of chronic changes in excretory needs, for example, to high or low sodium or potassium intake [1] and to acidosis and alkalosis [2]. One of the main functions the mammalian kidney assumes is the concentration of solutes in the urine. The diversity of mammals affords examples of renal adaptation to water conservation. Comparison among animals living in fresh water, in temperate regions, or inhabiting desert areas reveals several differences in kidney morphology and function [3]. Recent experiments have shown, not only among different species but within a given species as well, remarkable functional adaptation of the kidney to chronic variations in urine concentration. Urine concentration can be altered for sustained periods of time by modifying either antidiuretic hormone (ADH) or fluid intake. The Brattleboro rat offers a unique model in which the effects of the total absence of ADH can be studied [4]. By studying homozygous Brattleboro rats with diabetes insipidus (DI) and comparing their kidney function and morphology with that of heterozygous rats of the same strain, normal Long Evans rats (the strain from which the Brattleboro are derived), and DI rats chronically receiving antidiuretic hormone, we were able to demonstrate several features of the renal adaptation to water conservation. Several of these features were also observed in normal rats in response either to an increase or to a decrease in water intake for several weeks. These changes are described in the first part of this paper. The second part will address the mechanisms by which these changes are induced, and how they improve the urine concentrating process.

Rewarding and aversive effects of stimulant drugs in infant rats

Four experiments investigated the reinforcing effects of cocaine, amphetamine, and phenylpropanolamine using odor as the conditioned stimulus and infant rats as the subjects. At the age of 2 days the rats were injected with saline or with one of the three drugs and placed for 30 min in a plastic bag with almond-scented shavings. At the age of 18 days the rats were deprived of water for 12 hr and then given two tests that required different responses. In the consumption test they were given 30 min access to two water spouts, on surrounded by almond-scented cotton and the other surrounded by plain cotton. In the place test, they spent 5 min in a shuttle box with almond-scented shavings under one side and plain shavings under the other side. Compared to saline, all three drugs decreased water intake from the almond-scented spout and increased time spent over the almond-scented shavings.

Calcitonin effect on the dipsogenic response to intra-cerebroventricular administration of angiotensin II

Evidence indicates that intra-third cerebroventricular (III-ICV) administration of calcitonin suppresses food and water intake of rats. The purpose of this study was to determine whether calcitonin would influence angiotensin II-induced dipsogenesis when simultaneously administered III-ICV. Administration of calcitonin (0.5 U/rat) suppressed food and water intake in male Wistar rats. III-ICV administration of angiotensin II (100 ng/rat) to rats provided with ad lib food and water elicited short latency drinking without affecting food intake. III-ICV administration of calcitonin (0.5 U/rat) did not affect the drinking-inducing response to 100 ng/rat of angiotensin II when administered simultaneously. The results suggest that decrease in water intake by III-ICV calcitonin may be a consequence of the food intake suppression, i.e., reduced prandial drinking.

Effect of two-week infusion of deamino D-arginine vasopressin in rats.

Our purpose was to investigate a method of prolonged desmopressin (DDAVP) infusion in a free roaming rat to better understand the SIADH (syndrome of inappropriate antidiuretic hormone secretion) syndrome in man. DDAVP was infused for 2 weeks from implanted self-powered osmotic minipumps. At the end of that time, plasma DDAVP and urine osmolality were both significantly elevated in experimental as compared with control animals. However, hyponatremia and hypoosmolality, which are characteristic in the SIADH, did not develop. Our observations suggest that inappropriate high antidiuretic hormone levels do not necessarily lead to the SIADH either by urine sodium loss or by water retention if animals decrease water intake.

Increased food intake after opioid microinjections into nucleus accumbens and ventral tegmental area of rat

The nucleus accumbens (ACC) and ventral tegmental area (VTA), two areas believed to subserve reinforcement and increases in locomotor activity produced by opioid microinjections, were examined for their involvement in opioid-produced changes in ingestive behavior. Opioids were infused bilaterally, and food and water intakes were measured for 1 h thereafter. Different morphine doses were administered and, with placements in globus pallidus and lateral ventricles as controls for diffusion, it was found that only ACC and VTA microinjections (0.1–10 nmol) produced dose-related increases in food intake. In both the ACC and VTA low doeses of morphine also produced increases in water intake while in ACC high doses produced a decrease. Administration of morphine and an enkephalin analogue (Tyr- d-Met-Gly-Phe(4-NO 2)-Pro-NH 2) at different depths in the ACC indicated that the increase in food intake occurred at a site separate from that of the decrease in water intake. Using levorphanol, dextrorphan and morphine mixed with naloxone, it was shown that the effects were due to activation of opioid receptors. Additional experiments demonstrated that food intake is increased by ACC morphine under different levels of deprivation, with different times of testing and with availabilities of various goal objects in addition to food. The effect also did not appear to under go development of tolerance or sensitization. It was concluded that there are sites in the ACC and VTA where increased activity of endogenous opioid peptide systems reliably increase food intake and it was hypothesized that these sites may contribute to changes in ingestive behavior after systemic morphine administration. Also, together with other effects produced by opioid by opioid microinjections into the ACC and VTA, the present findings suggest that increased opioid activity in these areas produce a pattern of behaviors similar to that produced in normal animals by food conditioned stimuli.

Central and peripheral proglumide administration and cholecystokinin-induced satiety

Peripheral (50 mg/ml) or central (50 μg/μl) injections of proglumide were made into Sprague-Dawley rats which displayed satiety-like responses after the peripheral (100 μ/kg) or central (50 ng in 1 μl) administration of cholecystokinin (CCK). The satiety produced by CCK injection into the lateral hypothalamus, area postraema and ventromedial hypothalamus was significantly reversed by proglumide injections into these areas during a 4 h food intake test. Peripheral injection of proglumide after central or peripheral CCK injection did not modify this type of CCK-induced satiety. Central proglumide injection produced a reliable decrease in water intake and this is compatible with previous findings which describe the stimulation of water intake after central gastrin administration. These results suggest that various central and peripheral mechanisms which are involved in the regulation of appetite may function independently as a ‘failsafe’ system.

Continuously infused 2-amino-7-phosphonoheptanoic acid antagonizes N-methyl- d-aspartate-induced elevations of cyclic GMP in vivo in multiple brain areas and chemically-induced seizure activity

The effects of the chronic intracerebroventricular (i.c.v.) infusion of the potent dicarboxylic amino acid antagonist, 2-amino-7-phosphonoheptanoic acid (APH), were examined in female rats as a prelude to the use of this compound in exploring the role of dicarboxylic amino acids in barbiturate dependence and withdrawal. Doses of APH ranging from 2.7 to 54 μg/day were examined for signs of toxicity. Weight loss, decreased water intake and locomotor impairment were found only with the largest dose. No significant changes in consumption of food or body temperature were observed with any dose. The chronic administration of the drug (27 μg/day) blocked the elevation of the content of cyclic guanosine monophosphate induced by N-methyl- d-aspartate (NMDA) in all regions of the brain examined. The chronically-administered drug also blocked wild running behavior induced by the intracerebroventricular administration of two different drugs n-methyl- d-aspartic add and cyclohexylbarbiturate add. However, APH was ineffective in suppressing convulsions induced by the ED 50 dose of pentylenetetrazol given subcutaneously.

Neural lobe function in aged Wistar/Tw strain rats showing polydipsia and polyuria.

Neural lobe function in male rats of the Wistar/Tw strain was studied at 3, 7 and 16-18 months of age. A significant rise in the serum arginine vasopressin (AVP) level was noted in 16-18-month-old rats showing polydipsia and polyuria. The content and concentration of AVP in the neural lobe of aged rats were significantly less than those of younger animals (3 and 7 months). These results point out an enhancement of AVP release from the neural lobe of aged rats. The reduction in urinary volume in aged rats subjected to 24 hours of water deprivation was less than those in younger animals. No increase in urinary sodium, potassium and chloride concentrations was observed in aged rats, and the decrease in electrolyte excretion from urine during the dehydration period was less in aged rats than younger ones. These results suggest that the antidiuretic response to osmotic stimuli was reduced in aged rats. The administration of AVP to aged rats resulted in a significant decrease in water intake and urinary volume, but AVP administration did not induce any change in the electrolyte balance. Therefore, it is concluded that the main cause of the development of polydipsia and polyuria is the decline in renal function but not in neurosecretory activity, although exogenous AVP can effectively reduce water intake and urinary output in aged rats.

Teratogenicity study on 4-bromophenyl chloromethyl sulfone (BCS) in the rat.

To investigate the teratogenicity of 4-bromophenyl chloromethyl sulfone (BCS), doses of 0, 5, 35 and 245 mg/kg/day of the test substance were administered by oral gavage to Wistar-Imamichi rats from days 6 to 15 of gestation. The results were as follows: The treated dams did not exhibit any toxic symptoms or mortality attributable to the test substance. The following changes were noted in the treated dams: dose-dependent reduction of body weight gain and food intake in 35 and 245 mg/kg groups, and decreased water intake, reduced brain and thymus weights and increased relative weights of liver and kidney in the 245 mg/kg group. Fetal toxicity, increase of mortality and body weight depression, caused by the test substance was not observed. External, skeletal and visceral examination of the fetuses did not reveal any abnormalities ascribed to the test substance. With regard to ossification, the incidence of fetuses with delayed ossification of the 2nd and 5th sternebrae was significantly higher than in the control group. In summary, dams given BCS in doses of 35 mg/kg and 245 mg/kg displayed toxic manifestations. Fetuses showed slightly delayed ossification. However, the test substance was concluded to be free of any lethal or teratogenic effects.

Intraventricular administration of cyclo(His-Pro), a metabolite of thyrotropin-releasing hormone (TRH), decreases water intake in the rat.

We explored the effect of cyclo(His-Pro) on drinking in water-deprived rats. Intraventricular administration of cyclo(His-Pro) significantly reduced water intake in these rats in a dose-dependent fashion (3 X 10(-10) -3 X 10(-8) mole), whereas its intraperitoneal injection did not cause any effect on water intake. The inhibitory potency of cyclo(His-Pro) was found to be similar to that of thyrotropin-releasing hormone (TRH), but cyclo(His-Pro) did not significantly interfere with TRH binding in the rat brain. The data indicate that cyclo(His-Pro) action was not mediated through the TRH counterpart. These results suggest that cyclo(His-Pro) may play a potential role in the regulation of water intake in the rat brain.

Effect of Mixed Organic Acid Administration on Blood Levels of Chlortetracycline in Broiler Chicks

Male broiler chicks, when administered mixed organic acids via the drinking water for 3 days prior to water administration of chlortetracycline (CTC), showed no significant increases in the blood levels of the antibiotic. However, if the organic acids were administered simultaneously with the antibiotic, either via drinking water administration or via oral dosing, significant increases in the blood levels of the antibiotic were noted. With simultaneous administration of the antibiotic and mixed organic acids via the drinking water, a significant decrease in water intake was observed; however, in spite of the decrease in water intake and a concomitant decrease in CTC intake, significant increases in the blood levels of the CTC were still present.These data suggest that mixed organic acids, commonly used in the poultry industry, can be utilized to elicit an increase in CTC blood levels to a greater degree than would be anticipated without the use of the organic acids.

Decreased urinary active and inactive kallikrein by chronic infusion of vasopressin in conscious rats.

To assess possible interactions of circulating vasopressin with the synthesis or activation of renal kallikrein, we studied the effect of chronic infusion of vasopressin (7.2 U/kg/day i.p.) for 6 days on the urinary excretion of total and active kallikrein in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after the treatment with trypsin (200 micrograms/ml). Chronic infusion of vasopressin induced sustained decreases in urinary total, active and inactive kallikrein excretion, but did not affect the ratio of active to total kallikrein. The infusion of vasopressin induced significant increases in circulating levels of vasopressin (248.1 +/- 35.2 pg/ml in vasopressin-infused rats (n = 7) compared to 95.5 +/- 14.6 pg/ml in vehicle-infused rats (n = 7), p less than 0.001) and in weight gain (39.6 +/- 1.3 g in vasopressin-infused rats (n = 7) compared to 29.1 +/- 3.3 g in vehicle-infused rats (n = 7), p less than 0.05), and also sustained decreases in water intake and urine volume, but it did not induce any change in urinary sodium excretion. Circulating levels of angiotensin II was decreased by chronic infusion of vasopressin. Thus, the present study suggests that the elevation of circulating vasopressin levels induces a decrease in the synthesis of renal kallikrein.