Ingestion Of Solution Research Articles

Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats.

Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear. This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas. Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8% (v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing. The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls. The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors.

Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats

In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0–30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0–5% w/v) and saccharin (0–0.125% w/v) intake/preference. No net-flux in vivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

Synthesis and Biological Studies of a Novel CB1 Antagonist.

This paper describes the synthesis, early process development, salt selection strategies and pre clinical evaluation of novel, potent and selective CB1 antagonist, 8-Chloro-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-6-oxa-1,2-diaza-benzo[e]azulene-3-carboxylic acid piperidin-1-ylamide 1. The CB1 antagonism of compound 1 is also confirmed by reversal of CB1 agonist-induced hypothermia in Swiss albino mice. The process for the preparation of the compound 1 as a crystalline solid is also described. The crystalline form of the compound is found to be low bioavailable, therefore attempts have been made to improve its bioavailability through polymorphic transformation and salt formation. None of the salts prepared were found to be suitable for further development. The amorphous form of the compound 1 is found to be better suited. In vivo efficacy study of the amorphous form of compound 1 in 5% sucrose solution intake model in female Zucker fa/fa rats at single oral dose of 10 mg/kg demonstrates better reduction in the sucrose solution consumption than the corresponding crystalline form. The plasma concentration Cmax at AUC exposure of the amorphous form of the compound 1 is significantly improved and better than the Cmax of the corresponding crystalline form of the compound 1. On the basis of the efficacy, pharmacokinetic and toxicological evaluations, the compound 1 in the amorphous form is selected as a pre-clinical lead candidate.

Sucrose Solution Intake and its Schedule of Access Affect the Response to Chronic Variable Stress in Mice

There is a strong relationship between the intake of calorically-dense palatable food and stress. Moreover, intake of sodas is an important contributory factor to obesity, and is often associated with palatable food consumption. We studied the effects of 2-hour intermittent access to sucrose-sweetened water (SSW, 12.3%, soda-like) and its schedule of administration on the response to chronic variable stress in mice fed a high-fat, high-sugar diet. C57BL/6 mice received access to water or to both water and 2-hour SSW access during 5 weeks, in addition to their diet. After the first two weeks, half of the animals from each group were stressed daily using a chronic variable stress (CVS) paradigm, while the other half were kept undisturbed. During the CVS exposure period, SSW access was either scheduled randomly, right before the stressors or right after the stressor The effects of SSW and its schedule of administration on stress hormones, adiposity and serum lipids were analyzed. Results showed that SSW access induced an increase in energy intake, body weight gain and abdominal fat as well as attenuation in the response to CVS compared to water access alone. Moreover, there was a greater stress-relieving effect when SSW was administered after exposure to the stressors, compared to random exposure and exposure before the stressors. The present study provides arguments that the availability of intermittent SSW access renders mice more resilient to the effects of CVS, particularly when SSW is provided after exposure to stress.

Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

Lithium Toxicity Effects on Oxidative Stress, Dyslipidemia and Apoptosis in the Aged Rats

Aging is associated with metabolic changes and the development of diseases, due to the reduction of antioxidant defenses and alteration in apoptosis process. The lithium is used to treat bipolar disorder and neuroprotector; it also can be used as an antioxidant, but its function in aging has not been elucidated. The alterations in apoptosis could be associated with development oxidative stress in several tissues, although this information is unclear to aged rats. Disorders in apoptosis process and/or oxidative stress development impair the health of aged rats. The association between apoptosis with hepatic metabolism changes and oxidative stress disorder in aging is also unclear. Therefore, the objective of this work was to determine the effects of lithium on the lipid profile in serum and oxidative stress as well as apoptosis in the liver of aged rats. Twenty female Wistar rats were divided into 4 groups (n=5): the C group, with 3- month-old rats that received only water; the L group, with 3- month-old rats that received a lithium solution in drinking water; the S group, with 22- month-old rats that received water; and the SL group, with 22- month-old rats that received lithium in drinking water. The total experimental period was 30 days. All animals received standard diet ad libitum. The lithium dose took was according to neuroprotective dose and carefully monitored daily. The dyslipidemia studies were made through TC, HDL, LDL, VLDL, TG and glucose in serum. Oxidative stress analyses involved experiments with LH, TAS and ATP-SA. The apoptotic proteins analyses were made by western blot. Oxidative stress and apoptotic proteins were studied in the liver rats. The results showed that the lithium treatment reduced energy intake, aqueous solution intake and palatability in both, young and aged rats. This treatment increased TG and VLDL in the serum of animals in both groups. The treatment promoted hyperglycemia in young group, and in aged group, induced LDL enhanced as well as decreased HDL. Lithium induced enhanced Sirt 1 in livers of young and aged rats. TAS were higher in young group submitted lithium treatment. The livers of aged rats supplemented with lithium exhibited raised ATP- SA and Bax. In conclusion, the lithium induced dyslipidemia and hyperglycemia in the young, but this treatment also acted as a possible antioxidant agent, associated with Sirt 1 enhanced to protect this tissue of damages. In the aged rats, lithium promoted dyslipidemia and could induce cell death. Therefore, the supplementation could exert toxic effects in the livers of aged rats.

Effects of Electroacupuncture on Chronic Unpredictable Mild Stress Rats Depression-Like Behavior and Expression of p-ERK/ERK and p-P38/P38.

We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus.

Effects of perinatal methylphenidate (MPH) treatment on postweaning behaviors of male and female Sprague–Dawley rats

Methylphenidate (MPH) is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Thus, Sprague-Dawley rats were orally treated 3×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14mg/kg at each treatment time) on gestational days 6–21. All offspring/litter were orally treated with the same dose their dam had received on postnatal days (PNDs) 1–21. After weaning, offspring were assessed for adolescent play behavior, locomotor activity, motor coordination, Barnes maze performance, acoustic startle response, novel object recognition, residential running wheel activity, flavored solution intake, home cage behavior, water maze performance, elevated plus maze behavior, locomotor response to an MPH challenge, and passive avoidance. At euthanasia, whole brain and striatal weights as well as serum hormone levels were measured. Body weights of the high MPH group were reduced in both sexes. Males of the high MPH group were less active than control males in open field assessments on PNDs 40–42. Latency to maximum acoustic startle was significantly altered in females of the medium and high MPH groups and residential running wheel activity of females of the low and medium MPH groups was lower than control females. Open arm entries in the elevated plus maze were increased in subjects of the medium MPH group. Females of the low MPH group were less sensitive to the locomotor-increasing effects of an acute 5mg/kg MPH challenge. Serum hormone levels and whole brain and striatal weights were not altered by prior MPH treatment. These results indicate that MPH treatment during development has sporadic effects on postweaning behaviors and those effects were generally exhibited by females.

Carbohydrate-dependent, exercise-induced gastrointestinal distress.

Gastrointestinal (GI) problems are a common concern of athletes during intense exercise. Ultimately, these symptoms can impair performance and possibly prevent athletes from winning or even finishing a race. The main causes of GI problems during exercise are mechanical, ischemic and nutritional factors. Among the nutritional factors, a high intake of carbohydrate and hyperosmolar solutions increases GI problems. A number of nutritional manipulations have been proposed to minimize gastrointestinal symptoms, including the use of multiple transportable carbohydrates. This type of CHO intake increases the oxidation rates and can prevent the accumulation of carbohydrate in the intestine. Glucose (6%) or glucose plus fructose (8%–10%) beverages are recommended in order to increase CHO intake while avoiding the gastric emptying delay. Training the gut with high intake of CHO may increase absorption capacity and probably prevent GI distress. CHO mouth rinse may be a good strategy to enhance performance without using GI tract in exercises lasting less than an hour. Future strategies should be investigated comparing different CHO types, doses, and concentration in exercises with the same characteristics.

OR07-3 * SWEET TASTE ENHANCED SOME OF THE STIMULUS EFFECTS OF NICOTINE IN RODENTS

To evaluate non-pharmacological factors influencing smoking behavior, the effects of intake of sweet solutions on reinforcing and discriminative-stimulus effects of nicotine were examined in rodents. Methods. Effects of saccharin or glucose solutions, on (1) discriminative-stimulus effects were evaluated in male SD rats trained to discriminate 0.5 mg/kg nicotine, sc, from saline, and (2) reinforcing effects were evaluated by intravenous self-administration of nicotine (0.03 mg/kg/inj) under a progressive-ratio (PR) schedule in male SD rats, and by conditioned place preference (CPP) after 0.56 mg/kg nicotine in male C57/BL mice. Sweet solutions or water were freely available via drinking bottles for 5 min prior to the tests. Results. ED50 values for the discriminative-stimulus effects of nicotine after water (0.13 mg/kg) were decreased after 2% saccharin (0.09 mg/kg) while 0.2% saccharin and 3% glucose did not produce appreciable changes. However, the highest ratio values attained in the PR test were not significantly changed after 2% saccharin. In the CPP paradigm nicotine at 0.56 mg/kg did not produce significant preference, however after exposure to 1% saccharin a significant preference to the nicotine-paired compartment was induced. Conclusion. The present data suggest that sweet tastes can enhance the stimulus effects of nicotine under some circumstances.

Developmental treatment with ethinyl estradiol, but not bisphenol A, causes alterations in sexually dimorphic behaviors in male and female Sprague Dawley rats.

The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11-12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6-21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1-21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331-337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their behaviors were within the range of control males. Conversely, BPA treatment did not alter any measured endpoint. Similar to our previous reports (Ferguson, S. A., Law, C. D. Jr and Abshire, J. S. (2011) Developmental treatment with bisphenol A or ethinyl estradiol causes few alterations on early preweaning measures. Toxicol. Sci. 124, 149-160; Ferguson, S. A., Law, C. D. and Abshire, J. S. (2012) Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning. Neurotoxicol. Teratol. 34, 598-606), the BPA doses and design used here produced few alterations.

Decreased consumption of rewarding sucrose solutions after injection of melanocortins into the ventral tegmental area of rats.

The mesolimbic dopamine system is an important component of the neural circuitry controlling reward-related behavior. We have recently shown that the melanocortin peptides decrease normal homeostatic feeding through actions in the ventral tegmental area. It is unknown, however, whether melanocortin peptides can also act on dopamine pathways to regulate hedonic, reward-related aspects of feeding. In these studies, we tested whether injection of melanocortin receptor agonists directly into the ventral tegmental area (VTA) affected the intake of appetizing and rewarding sugar solutions in two-bottle choice tests. Varying doses of the melanocortin receptor agonist, MTII, were injected into the VTA, and the intake of different sugar solutions was measured in two-bottle choice tests to distinguish between potential effects on homeostatic versus hedonic aspects of feeding. In addition, 24-h food intake was measured throughout the experiments. Injection of MTII into the VTA dose dependently decreased the intake of 1 and 2 % sucrose solutions and 0.2 % saccharin solutions and decreased 24-h food intake in each study. Although MTII also decreased the intake of a 10 % sucrose solution, MTII appeared to be less potent in rats exposed to 10 % sucrose, as only the highest dose of MTII tested was effective at reducing 10 % sucrose intake and food intake in these rats. These studies demonstrate that melanocortins can act directly in the VTA to control reward-related feeding. Thus, these studies add to the growing body of evidence showing that melanocortins can interact with the mesolimbic dopamine system to regulate multiple reward-related behaviors.

Blockade of central delta-opioid receptors inhibits salt appetite in sodium-depleted rats

Various studies have investigated the role of central opioid peptides in feeding behavior; however, only a few have addressed the participation of opioids in the control of salt appetite. The present study investigated the effect of intracerebroventricular injections of the δ-opioid antagonist, naltrindole (5, 10 and 20nmol/rat) and the agonist, deltorphin II (2.5, 5, 10 and 20nmol/rat) on salt intake. Two protocols for inducing salt intake were used: sodium-depletion and the central injection of angiotensin II. In addition, the effect of a central δ-opioid receptor blockade on locomotor activity, on palatable solution intake (0.1% saccharin) and on blood pressure was also studied. The blockade of central δ-opioid receptors inhibits salt intake in sodium-depleted rats, while the pharmacological stimulation of these receptors increases salt intake in sodium-replete animals. Furthermore, the blockade of central δ-opioid receptors inhibits salt intake induced by central angiotensinergic stimulation. These data suggest that during sodium-depletion activation of the δ-opioid receptors regulates salt appetite to correct the sodium imbalance and it is possible that an interaction between opioidergic and angiotensinergic brain system participates in this control. Under normonatremic conditions, δ-opioid receptors may be necessary to modulate sodium intake, a response that could be mediated by angiotensin II. The decrease in salt intake following central δ-opioid receptors blockade does not appear to be due to a general inhibition of locomotor activity, changes in palatability or in blood pressure.

The role of serotonin in feeding and gut contractions in the honeybee

Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of feeding and digestion in many animals from worms to mammals. In insects, 5-HT functions both as a neurotransmitter and as a systemic hormone. Here we tested its role as a neurotransmitter in feeding and crop contractions and its role as a systemic hormone that affected feeding in adult foraging honeybees. We found 5-HT immunoreactive processes throughout the gut, including on the surface of the oesophagus, crop, proventriculus, and the midgut, as well as in the ventral nerve cord. mRNA transcripts for all four of the known bee 5-HT receptors (Am5-ht1A,2α,2β,7) were expressed in the crop and the midgut suggesting a functional role for 5-HT in these locations. Application of a cocktail of antagonists with activity against these known receptors to the entire gut in vivo reduced the rate of spontaneous contraction in the crop and proventriculus. Although feeding with sucrose caused a small elevation of endogenous 5-HT levels in the haemolymph, injection of exogenous 5-HT directly into the abdomen of the bee to elevate 5-HT in the haemolymph did not alter food intake. However, when 5-HT was injected into directly into the brain there was a reduction in intake of carbohydrate, amino acid, or toxin-laced food solutions. Our data demonstrate that 5-HT inhibits feeding in the brain and excites muscle contractions in the gut, but general elevation of 5-HT in the bee’s haemolymph does not affect food intake.

A multi-generational study on low-dose BPA exposure in Wistar rats: Effects on maternal behavior, flavor intake and development

Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats.BPA was orally administered at a daily dose of 5μg/kg body weight to F0 pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to F1 offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as “non-maternal” behaviors in F0 and F1 dams from parturition until LD 8. The flavor preferences of F1 and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21–34 and PND 86–99.BPA exposure: 1) decreased maternal behavior in F1 dams, 2) caused developmental defects in both F1 and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in F1, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change.Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure.

Experience with Sugar Modifies Behavioral but not Taste-Evoked Medullary Responses to Sweeteners in Mice

Dietary exposure to sugars increases the preference for and intake of sugar solutions in mice. We used brief-access lick tests and multiunit electrophysiological recordings from the nucleus of the solitary tract (NST) to investigate the role of taste in diet-induced changes in sucrose responsiveness. We exposed C57BL/6J (B6) and 129X1/SvJ (129) mice to either a sucrose diet (chow, water, and a 500mM sucrose solution) or a control diet (chow and water) for 3 days. In B6 mice, exposure to the sucrose diet decreased the appetitive response (i.e., number of trials initiated) but had no effect on the consummatory response (i.e., rate of licking) to 500mM sucrose and 20mM saccharin. In 129 mice, exposure to the sucrose diet increased the appetitive response but had no effect on the consummatory response to the sweetener solutions. In the NST recordings, the B6 mice exhibited larger multiunit responses to sweeteners than 129 mice, but there was no effect of the sucrose diet in either strain. Our results indicate that sucrose exposure alters the appetitive response of B6 and 129 mice to sweeteners in diametrically opposed ways and that these changes are mediated by structures in the gustatory neuraxis above the NST (e.g., ventral forebrain).

Oxytocin receptor blockade reduces acquisition but not retrieval of taste aversion and blunts responsiveness of amygdala neurons to an aversive stimulus

When gastrointestinal sickness induced by toxin injection is associated with exposure to novel food, the animal acquires a conditioned taste aversion (CTA). Malaise is accompanied by a surge in oxytocin release and in oxytocin neuronal activity; however, it is unclear whether oxytocin is a key facilitator of aversion or merely its marker. Herein we investigated whether blockade of the oxytocin receptor with the blood–brain barrier penetrant oxytocin receptor antagonist L-368,899 is detrimental for the acquisition and/or retrieval of lithium chloride (LiCl)-dependent CTA to a saccharin solution in mice. We also examined whether L-368,899 given prior to LiCl affects neuronal activity defined through c-Fos immunohistochemistry in select brain sites facilitating CTA acquisition. L-368,899 given prior to LiCl caused a 30% increase in saccharin solution intake in a two-bottle test, but when the antagonist was administered before the two-bottle test, it failed to diminish the retrieval of an existing CTA. LiCl administration increased c-Fos expression in the hypothalamic paraventricular and supraoptic nuclei, area postrema, nucleus of the solitary tract and basolateral and central (CNA) nuclei of the amygdala. L-368,899 injected before LiCl reduced the number of c-Fos positive CNA neurons and brought it down to levels similar to those observed in mice treated only with L-368,899. We conclude that oxytocin is one of the key components in acquisition of LiCl-induced CTA and the aversive response can be alleviated by the oxytocin receptor blockade. Oxytocin receptor antagonism blunts responsiveness of CNA to peripherally injected LiCl.

Preoperative oral rehydration solution intake volume does not affect relative change of mean arterial blood pressure and crystalloid redistribution during general anesthesia in low-risk patients: an observational cohort study

Despite the implementation of liberal preoperative fasting routines, it is unclear whether preoperative oral rehydration solution intake volume affects blood pressure during general anesthesia. We enrolled 60 patients (American Society of Anesthesiologists status I/II) undergoing tympanoplasty. Patients drank 200-1,000 ml oral rehydration solution until 2-3 h before anesthesia induction. Anesthesia was induced by propofol and maintained with sevoflurane and remifentanil. Coinciding with anesthesia induction, 15 ml/kg Ringer's acetate solution was administered intravenously over 60 min followed by 1 ml/kg Ringer's acetate solution over the next 30 min. Mean arterial blood pressure (MAP) and whole-body bioelectrical resistance for extracellular fluid (R e) during anesthesia were compared between retrospectively classified intake groups of oral rehydration solution. There were no differences in mean MAP during the 30-90 min period relative to baseline [0.67 (0.60-0.74), 0.65 (0.61-0.76), 0.64 (0.60-0.70), P = 0.96] and relative R e at 90 min [0.945 (0.018), 0.944 (0.021), 0.943 (0.021), P = 0.95] between the small (n = 14), intermediate (n = 29), and large (n = 17) intake groups. The intake volume of preoperative oral rehydration solution does not affect the magnitude of hypotension during general anesthesia in low-risk patients undergoing minor surgery.

The effect of sugar solution type, sugar concentration and viscosity on the imbibition and energy intake rate of bumblebees

Nectar is an essential resource for bumblebees and many other flower-visiting insects. The main constituents of nectar are sugars, which vary in both composition and concentration between plant species. We assessed the influence of sugar concentration, sugar solution viscosity and sugar solution composition on the imbibition and energy intake rate of bumblebees, Bombus impatiens Cresson (Hymenoptera: Apidae). To do this, we measured their rate of solution intake for 49 different sugar solution treatments, which varied in both sugar composition and concentration. In general, the imbibition rates of bumblebees were found to increase with increasing sugar concentration, probably due to their preference for high sugar concentrations, up to a concentration of 27% (w/w), at which point solutions reached a threshold viscosity of approximately 1.5–1.6mPa.s. Above this threshold, the increasing viscosity of the solutions physically inhibited the imbibition rates of bees, and imbibition rate began to decrease as the concentration increased. Nevertheless, bumblebee energy intake rate increased with increasing concentration up to about 42–56%. Although we found that sugar solution composition had an impact on both imbibition and energy intake rate, its effect was not as straightforward as that of sugar concentration and viscosity.

Subdiaphragmatic vagotomy reduces intake of sweet-tasting solutions in rats.

Studies have shown that there are strong interactions between gustatory and visceral sensations in the central nervous system when rats ingest sweet foods or solutions. To investigate the role of the subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats deprived of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water.