Sham Drinking Research Articles

Suspected intoxication by Kikuyu grass (Cenchrus clandestinus) of dairy cattle in the Azores, Portugal

ABSTRACT Case history An outbreak of suspected Kikuyu grass (Cenchrus clandestinus) intoxication among dairy cattle occurred on the island of Terceira in the Azores (Portugal), in October 2022. The animals affected were non-lactating dairy cows and heifers from five small farms grazing (free or tethered) a Kikuyu-dominant pasture. Of the 29 animals exposed, 17 were affected, and eight (five heifers and three adult cows) died, resulting in a morbidity rate of 58%, a mortality rate of 28% and a case mortality rate of 47%. Clinical findings and treatment The clinical signs were non-specific and inconsistent, and included dry faeces, some with dark red blood; apathy and prostration; abdominal dilatation; tachycardia; tachypnoea; pale or jaundiced mucous membranes; sham drinking; sialorrhoea; and moderate to severe dehydration. Symptomatic treatment was provided but was ineffective. Haematology and serum biochemistry revealed an acute inflammatory leukogram, increased alkaline phosphatase (ALP) activity, decreased gamma-glutamyl transferase (GGT) activity, and azotaemia. The most consistent necropsy findings were haemorrhages in the epicardium and endocardium, an enlarged liver with rounded edges, non-perforated abomasal ulcers, and haemorrhagic lesions in the small and large intestines. Histopathology indicated myocarditis, hepatitis, interstitial nephritis, enteritis and colitis. Several fungal species were isolated from grass samples taken from affected pastures including several Fusarium spp., the genus implicated in Kikuyu toxicosis. Immediate removal of the animals from the pasture with Kikuyu was the only measure that prevented new cases and resulted in the recovery of some of the less affected animals. Diagnosis The epidemiological features of this outbreak and the clinical signs and micro– and macroscopic lesions observed were highly suggestive of Kikuyu grass poisoning. Clinical relevance Although the weather conditions varied from other published cases, the grazing conditions (almost exclusive Kikuyu grass) and the post-mortem findings were very similar to those described in the literature, particularly the haemorrhages in the epicardium and endocardium. Kikuyu grass is very invasive and presents many desirable characteristics as cattle feed. Thus, an increase in cases of intoxication may be expected. Practitioners and farmers in areas where Kikuyu grass is abundant should be aware of the potential risks of grazing cattle exclusively on these pastures. They should also be aware of the early and subtle signs of Kikuyu intoxication to allow for timely removal of the animals from pasture.

Water-induced thermogenesis and fat oxidation: a reassessment.

Background/Objectives:Drinking large amounts of water is often recommended for weight control. Whether water intake stimulates energy and fat metabolism is, however, controversial with some studies reporting that drinking half a litre or more of water increases resting energy expenditure (REE) by 10–30% and decreases respiratory quotient (RQ), whereas others report no significant changes in REE or RQ. The aim here was to reassess the concept of water-induced thermogenesis and fat oxidation in humans, with particular focus on interindividual variability in REE and RQ responses, comparison with a time-control Sham drink, and on the potential impact of gender, body composition and abdominal adiposity.Subjects/Methods:REE and RQ were measured in healthy young adults (n=27; body mass index range: 18.5–33.9 kg m−2), by ventilated hood indirect calorimetry for at least 30 min before and 130 min after ingesting 500 ml of purified (distilled) water at 21–22 °C or after Sham drinking, in a randomized cross-over design. Body composition and abdominal fat were assessed by bioimpedance techniques.Results:Drinking 500 ml of distilled water led to marginal increases in REE (<3% above baseline), independently of gender, but which were not significantly different from Sham drinking. RQ was found to fall after the water drink, independently of gender, but it also diminished to a similar extent in response to sham drinking. Interindividual variability in REE and RQ responses was not associated with body fatness, central adiposity or fat-free mass.Conclusions:This study conducted in young men and women varying widely in adiposity, comparing the ingestion of distilled water to Sham drinking, suggests that ingestion of purified water per se does not result in the stimulation of thermogenesis or fat oxidation.

In this issue

In this issue

Amiloride-sensitive sodium signals and salt appetite: multiple gustatory pathways.

In the rat, the ionic specificity of Na+ appetite is thought to rely on amiloride-sensitive Na+ signals conveyed by the chorda tympani (CT) nerve. We evaluated whether robust Na+ appetite relies exclusively on CT-mediated amiloride-sensitive Na+ signals. Amiloride dramatically reduced sham drinking of NaCl (41.9 +/- 9.0 vs. 6.9 +/- 3.7 ml, 0.1 M NaCl without vs. with 100 microM amiloride), which resulted in intake that was not different from intake of a non-Na+ salt solution (8.8 +/- 2.3 ml, 0.15 M KCl). In addition, intake of 0.1 M NaCl in CT-transected (CTX) rats was reduced (35.8 +/- 13.3 vs. 8.67 +/- 3.4 ml, sham-operated vs. CTX rats), but the addition of amiloride (100 microM) further reduced intake in CTX rats (0.5 +/- 0.29 ml). These data support the idea that amiloride-sensitive Na+ channels are the critical gustatory substrate for Na+ identification during Na+ appetite in the rat. However, the data indicate that these amiloride-sensitive signals are not conveyed exclusively by the CT nerve but by an additional afferent pathway.

Differential effects of intraventricular injections of tachychinin NK-sub-1 and NK-sub-3 receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

The effects of lateral ventricular injections of succinyl-[Asp6, N-Me-Phe8]-substance P (SENK; 25, 100, 200 ng), a tachykinin NK3 receptor agonist, and [Sar9, Met(O2)11]-substance P (Sar Met; 100, 200 ng), an NK1 receptor agonist, on normal (gastric fistula closed) and sham drinking (gastric fistula open) of hypertonic NaCl by sodium-deficient rats were compared. Intraventricular injections of Sar Met had no effect on NaCl intake in either condition. Injections of 100 ng and 200 ng SENK caused an equal suppression of NaCl intake in the 2 fistula conditions. The latency to drink was not affected, but the initial lick rate was significantly lower and decayed more rapidly after 100 ng SENK than after saline or 25 ng SENK. The results show that (a) the tachykinin subtypes are not equally involved in the control of need-induced salt intake; (b) negative feedback from the stomach and distal gastrointestinal tract is not required for intraventricular injections of SENK to suppress sodium appetite; (c) the activation of NK3 receptors decreases the oral excitatory influence of hypertonic NaCl in sodium-deficient rats.

Differential effects of intraventricular injections of tachychinin NK₁ and NK₃ receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

Differential effects of intraventricular injections of tachychinin NK₁ and NK₃ receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

Behaviorally specific inhibition of sham feeding by amylin

To further characterize amylin’s inhibitory action on feeding, we examined the effects of intraperitoneal injections of amylin on sham feeding of sucrose in food-deprived male rats with chronic gastric cannulas. Thirty and 100 μg/kg amylin reduced sham feeding, but did not terminate it or elicit the behavioral sequence of satiety. Real feeding of sucrose, but not sham feeding, was reduced after injection of 10 μg/kg amylin. Amylin’s inhibitory effect on sham feeding appeared behaviorally specific because neither 30 nor 100 μg/kg amylin affected sham drinking of water in thirsty rats and because no abnormal behaviors occurred. We conclude that amylin has a behaviorally specific satiating effect on sucrose sham feeding that is insufficient to elicit satiety in absence of gastric or postgastric food stimulation.

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

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

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 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.

Different central opioid receptor subtype antagonists modify maltose dextrin and deprivation-induced water intake in sham feeding and sham drinking rats

Different central opioid receptor subtypes participate in the mediation of intakes of simple (sucrose: μ, κ 1 and complex (maltose dextrin: μ) carbohydrates as well as deprivation-induced water intake (μ) under real-feeding and real-drinking conditions. An identical pattern of μ and κ 1 mediation of sucrose intake was observed in sham-feeding rats as well, suggesting their actions on orosensory mechanisms supporting sucose intake. The present study examined whether centrally administered general (naltrexone: 1–50 μg), μ (β-funaltrexamine: 1–20 μg), μ 1 (naloxonazine: 50 μg), κ 1 (nor-binaltorphamine: 1–20 μg), δ 1 ([ d-Ala 2, Leu 5, Cys 6]-enkephalin: 10–40 μg) or δ 22 (naltrindole isothiocyanate: 20 μg) opioid subtype antagonists altered either maltose dextrin (10%) intake during sham feeding or deprivation (24 h)-induced water intake during sham drinking in rats with gastric fistulas. Sham feeding significantly increased maltose dextrin intake (180%) and sham drinking significantly increased deprivation-induced water intake (256%) over a 60 min time course. Naltrexone significantly and dose-dependently reduced maltose dextrin intake (78%) in sham feeding rats, and deprivation-induced water intake (51%) in sham drinking rats. Maltose dextrin intake in sham feeding rats was significantly reduced by either κ 1 (69%) or δ 1 (59%) opioid antagonism, was significantly increased by μ 1 antagonism (43%), and was not significantly affected by either μ or δ 2 opioid antagonism. Deprivation-induced water intake in sham drinking rats was significantly reduced by either μ (41%), μ 1 (28%), δ 1 (48%) or δ 8 (28%) opioid antagonism, but was not significantly affected by κ 1 opioid antagonism. The difference in opioid receptor subtype mediation of maltose dextrin intake in real feeding and sham feeding conditions suggest that κ 1 and δ 1 receptors are involved in the orosensory mechanisms supporting maltose dextrin intake, while μ receptors are involved in the ingestive and post-ingestive mechanisms supporting maltose dextrin intake. The different patterns of opioid involvement in sucrose and maltose dextrin intake in sham feeding and real feeding conditions provide further support for the hypothesis that at least two different carbohydrate taste systems exist. The difference in opioid receptor subtype mediation of deprivation-induced water intake in real drinking and sham drinking conditions may reflect the removal in the sham drinking condition of a μ-mediated prerestorative satiety mechanism, and the unmasking of other opioid-mediated signalling mechanisms.

Mammalian Bombesin-Like Peptides Suppress Sham Drinking of Salt by Sodium-Deficient Rats

Bombesin (BN) and its mammalian relatives, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have been implicated in the control of food intake, and more recently systemic injections of BN have been shown to suppress need-free and sodium deficiency-induced salt (NaCl) intake. Postoral mechanisms that are activated by the ingestion of salt contribute to the termination of salt intake. The hypothesis that BN-like peptides potentiate postoral salt ingestion-contingent feedback and thereby accelerate the termination of salt intake was evaluated by measuring the effects of peripheral injections of BN (4, 6, 16 μg/kg), GRP (4, 8, 16 μg/kg), and NMB (4, 8, 16 μg/kg) on sham (gastric fistula open) and normal (gastric fistula closed) drinking of NaCl (0.5 M ) by sodium-deficient male rats. Sodium deficiency was induced by injections of deoxycorticosterone acetate and furosemide. Injections of 4 μg/kg BN produced a transient suppression in the sham drinking of salt and a more sustained reduction of salt intake when postoral factors were present in the normal drinking condition. In contrast, injections of 6 and 16 μg/kg BN produced the same pronounced suppression in salt intake in both the closed and open fistula test conditions. Only 16 μg/kg GRP was behaviorally effective, and this dose reliably suppressed both normal and sham drinking of salt. On an equimolar basis, BN was more potent than GRP. Injections of NMB had no effect on salt intake under any dose or fistula condition. The order of BN-like peptide potency in suppressing sham and normal drinking of salt by sodium-deficient rats (BN > GRP > NMB) is similar to the peptides' effects on feeding. When postoral feedback is minimized, the combination of BN or GRP and pregastric stimuli mimic the salt intake by rats in the fistula closed, normal drinking condition.

Pregastric and postabsorptive inhibitory effects of water on angiotensin-induced Fos in rat brain

Intraventricularly (ICV)-injected Ang II activates cells in several forebrain structures of rats, including SFO, OVLT, PVN and SON, and produces a spectrum of physiological and behavioral responses. It has been reported that the Fos-like immunoreactivity (FLI; a marker of cell activation) that is induced in PVN and SON by exogenous Ang II is prevented by allowing rats to ingest water after injection. The present study tests whether this inhibitory effect of water is due to either preabsorptive (oral) or postingestive factors, or both. Rats received cerebroventricular injection of Ang II (100 ng) and were killed 1 h later. One group received no water after the injection, another group drank water, a third group drank water but had it drain from a gastric fistula (sham drinking), and a fourth group received an intragastric infusion of water. In confirmation of a previous study, rats allowed to drink water after Ang II showed an almost complete absence of FLI in SON and PVN, compared with those not allowed access to water. Both sham drinking and intragastrically-infused rats showed less FLI in SON and PVN than nondrinkers. The reduction was greater in the infused group than the sham drinkers, but was not as great as in those allowed to drink water and absorb it. This suggests that both orally-mediated as well as postabsorptive factors can inhibit Ang II-induced FLI by impinging upon cells in the SON and PVN. In contrast, Ang II-induced FLI in OVLT and SFO was not affected by any of the oral or gastric water conditions.

Preference for nacl solutions in sham drinking Sprague-Dawley rats: Water deprivation, sodium depletion, and angiotensin II

Male Sprague-Dawley rats were fitted with closable gastric fistulas and were then tested under closed fistula (real intake) and open fistula (sham intake-fluids drain from the stomach without appreciable absorption) conditions in one of three states: fluid deprivation, sodium depletion, and infusion of angiotensin (Ang) II. Water and various concentrations of NaCl were offered to drink in 1-h one- or two-bottle intake tests. In Experiment 1, water-deprived rats with closed fistulas drank more 0.15 M NaCl than either water or 0.3 M NaCl, offered in one-bottle tests. In sham drinking tests, the intake decreased monotonically as NaCl concentration increased. In two-bottle tests, water was greatly preferred over NaCl solutions. In Experiment 2, sodium-depleted rats preferred NaCl over water, again demonstrating a peak intake at 0.15 M in closed fistula conditions. However, with the fistula open the intakes of 0.05 and 0.15 M were similar, and 0.45 M considerably lower. In Experiment 3, Ang II-infused rats consumed both water and NaCl in two-bottle tests in both open and closed fistula trials. The quantity ingested on sham trials was only modestly elevated over real intake trials with Ang lI compared with sham tests in Experiments 1 and 2.

Sham intake of ethanol in “P” rats

Alcohol-preferring (P) rats were surgically fitted with gastric fistulas, and intakes of 10% ethanol solution were measured in 1-h sessions either with the fistula closed (normal drinking) or open (sham drinking). In water-replete P rats in which ethanol access was limited to 1 h/day, no increase in intake was noted in the sham compared with normal drinking tests in the day. A small increase was seen when the sham drinking test was conducted at night. In water-deprived P rats, sham intake of ethanol was elevated over intakes in closed fistula trials. However, in comparison with water intake on separate test days, sham intake of ethanol by P rats was lower and satiated after 15–30 min. The absence of robust sham alcohol drinking in P rats is similar to what we have previously reported in normal Sprague-Dawley rats, suggesting that preabsorptive factors alone do not account for the strain differences in ethanol preference.

Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats

Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-min consumption of sweetened milk after overnight deprivation whether the cannulae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 μmol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30-min testing session. However, 5-HT failed to elicit resting—the terminal behavioral phase of satiety—in sham-feeding rats. Direct comparison of the effects of 4.0 μmol/kg 5-HT under both feeding conditions established that this dose promoted resting only when rats fed with their cannulae closed. The actions of 5-HT on feeding and resting were behaviorally selective because serotonergic treatment did not retard the beginning of feeding, alter sham drinking of water, or reduce investigation by food-deprived rats of a novel object in an open field. Together, the results suggest that 5-HT exerts separate actions to inhibit feeding and accelerate the process of satiation as marked by resting. However, peripheral 5-HT is inadequate as a signal for modulating satiety in the absence of postingestive stimuli.

Sham ingestion of alcohol in rats

Sprague-Dawley rats were surgically fitted with gastric fistulas and their intakes of 6% ethanol measured first with the fistula closed (normal drinking) and then on three test sessions with the fistula open (sham drinking). The rats were water deprived prior to the 1-h test sessions. On the second and third sham drinking sessions, intakes of alcohol were significantly increased above those in both the closed and first open fistula session. The effectiveness of the sham ingestion preparation to minimize absorption was shown by the much lower blood alcohol levels in sham compared with real drinking rats. Thus, reduction of the postingestive effects of alcohol leads to an acquisition of increased oral consumption. The similarities and differences between sham intakes of water and alcohol are discussed.

Similar effect of raclopride and reduced sucrose concentration on the microstructure of sucrose sham feeding

Raclopride, a dopamine D 2 antagonist, decreases the intake of sucrose solutions during sham feeding tests and of water during sham drinking tests in rats. To determine whether the reduced intake of sucrose by raclopride was due to a decrease in the positive reinforcing effect of sucrose or to an impairment in licking movements, we compared the rate, efficiency and pattern of licking after two procedures each of which decreased sucrose sham intake about 50%; these were (a) pretreatment with raclopride (ID 50), and (b) dilution of the sucrose concentration sham fed from 10 to 5%. Microstructural analysis failed to reveal significant differences in the rate, efficiency (licks/ml) or patterns of licking between these two procedures. When raclopride inhibited the sham drinking of water, the rate and efficiency of licking were normal, but the patterns of licking were qualitatively different from those observed when raclopride inhibited the sham feeding of sucrose. We conclude that raclopride decreases intake of 10% sucrose during sham feeding and intake of water during sham drinking by decreasing the positive reinforcing potency of the orosensory effect(s) of the two liquids on licking rather than by decreasing the ability to lick. These results provide strong evidence that interaction of dopamine at D 2 receptors is necessary for the normal sensory and/or hedonic processing of the orosensory stimuli produced by sucrose during sham feeding and by water during sham drinking.

Intraduodenal infusions of fats elicit satiety in sham-feeding rats

The satiating effect of duodenally administered fats was investigated with intraduodenal infusions of Intralipid in sham-feeding rats. Intralipid rapidly inhibited sham feeding and elicited the behavioral sequence of satiety. The satiating potency of Intralipid infusions in concentrations of 0.125-1 kcal/ml was a function of the concentration infused. The time course for Intralipid-induced satiety showed that fats inhibited feeding and led to the behavioral sequence of satiety within 15 min after the infusions began. This time course is evidence for a preabsorptive site of action to the small intestine. To test this hypothesis we added the local anesthetic tetracaine to Intralipid infusions. Tetracaine significantly reduced the satiating potency of Intralipid infusion. This result supports the hypothesis of a preabsorptive site of action. We also tested the specificity of intraduodenal Intralipid for feeding by administering Intralipid to rats that were sham drinking. The effect of Intralipid was relatively specific because the threshold concentration of Intralipid necessary to inhibit sham drinking was higher than the threshold for sham feeding. In addition, at superthreshold concentrations, Intralipid inhibited sham drinking less than sham feeding and elicited different behaviors than were observed during sham feeding.

Sham drinking in rats: Osmotic and volumetric manipulations

Male rats, fitted with indwelling gastric fistulas, were tested with either a closed fistula (normal drinking) or an open fistula (sham drinking) following either intracellular dehydration (with NaCl), extracellular dehydration (with PEG), or the combination of the two stimuli. In normal drinking tests, the combined stimulus induced an intake of water that was the sum of the individual effects. In sham-drinking tests, both NaCl- and PEG-treated rats drank up to twice that of their normal drinking counterparts, but those given NaCl + PEG showed no such increase. Various body fluid measurements confirmed the persistence of the respective dehydration states at the end of sham-drinking sessions. The relatively poor or absent sham drinks after these stimuli are contrasted with vigorous sham drinking following fluid deprivation. In a second experiment, sham drinking following NaCl injections did not improve with repeated testing, but intake after intravenous infusion of NaCl did show some increase but was still modest and slow compared with that after fluid deprivation.

Effects of 5-hydroxytryptamine and [formula omitted] on sham feeding and sham drinking in the gastric-fistulated rat

Previous experiments indicated that drug treatments which increase serotonergic activity produce dose-related reductions in sucrose sham feeding. In the present studies, 5-hydroxytryptamine (5-HT, 2 mg/kg, IP) significantly reduced sham feeding; its effect was reversed by the peripheral 5-HT receptor antagonist, xylamidine (3 mg/kg, IP). At the same dose, 5-HT did not affect water sham drinking. These are the first data to implicate serotonergic activity at peripherally located 5-HT receptors in the modulation of sucrose sham feeding. d- Fenfluramine (3 mg/kg, IP) also reduced sham feeding, an effect that was weakly attenuated by xylamidine, suggesting substantial mediation of its effect by centrally located 5-HT receptors. Sham drinking was reduced by d- fenfluramine (3 mg/kg), although to a lesser degree. In comparison with the previous studies, the present data suggest that in smaller doses d- fenfluramine is relatively selective in its effect on sham feeding, but that, in larger doses, the selectivity may be lost.