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Role of angiotensin in sodium appetite of sodium-deplete sheep.

The role of the renin-angiotensin system (RAS) in the Na appetite of Na-deplete sheep was investigated. Intravenous infusion of the angiotensin-converting enzyme inhibitor, captopril, at 0.01 or 0.1 mg X kg-1 X h-1 did not cause any change in Na intake, although the higher dose caused a marked decrease in mean arterial blood pressure. Intravenous infusion of captopril at 1.0 mg X kg-1 X h-1 over 24 h decreased Na intake by 45-55% in the absence of any change in Na loss. The decrease in Na intake was restored to base-line level or above by concurrent intravenous infusion of angiotensin II (ANG II) at 3.8 or 24 micrograms/h over 24 h but not by intracerebroventricular (ICV) ANG II at 3.8 micrograms/h. In addition, ICV infusion of 0.7 M mannitol (1 ml/h over 3 h), which reduced cerebrospinal fluid (CSF) and brain extracellular fluid [Na], still increased Na intake when combined with intravenous captopril. Water intake was not altered during intravenous captopril or ANG II alone but was increased during ICV ANG II or 0.7 M mannitol (with or without iv captopril). In conclusion, these results suggest that the RAS is involved in the Na appetite of the Na-deplete sheep. Furthermore, it would appear that the brain area involved is one without a blood-brain barrier but with a CSF-brain barrier, such as one of the circumventricular organs. Also, it would appear that the effect of lowered cerebral Na and the effect of activation of the renin-angiotensin system on Na appetite are independent.

Angiotensin II↗

Sex offending and sexual appetite: the clinical and theoretical relevance of hypersexual desire.

Disinhibited sexual desire, clinically manifested as hypersexual desire disorders, can be operationally defined by considering three behavioral domains associated with sexual motivation or appetitive behavior: (a) sexual preoccupation (time/day consumed by fantasies, urges, and activities), (b) the repetitive frequency of enacted sexual behavior (total sexual outlet/week), and (c) adverse consequences associated with repetitive sexual behavior: Data are presented suggesting that clinical samples of males with paraphilias, paraphilia-related disorders, and sexual coercion may be associated with disinhibited sexual appetite. These conditions need to be addressed by an integrated combination of psychotherapeutic and psychopharmacologic interventions that specifically target disinhibited sexual appetitive behaviors, their antecedents, and consequences. Although combination therapies (empirically based specific psychotherapies in conjunction with psychopharmacological treatments) have demonstrated superior efficacy in many Axis I psychiatric disorders, such combination therapies to reduce paraphilias, paraphilia-related disorders, and adult sexual coercion are currently underutilized in both North and South America and Europe.

Adult↗

Effect of chronic administration of deoxycorticosterone acetate on salt appetite of captopril-treated rats.

Chronic dietary administration of the angiotensin I-converting enzyme inhibitor, captopril (1.0 g/kg food), induced an appetite for 0.15 M NaCl solution relative to distilled water in a two-bottle ad libitum access paradigm. Graded doses of deoxycorticosterone acetate (DOCA) were administered to the captopril-treated rats via Silastic tubes implanted sc. A U-shaped dose-response relationship was observed between dose of DOCA and intake of 0.15 M NaCl solution. The lowest intake of NaCl occurred with a dose of 102.1 micrograms DOCA/day (333 micrograms/kg X day). Water and food intakes were not affected significantly. At the end of the first week of treatment with DOCA, pilocarpine (3.0 mg/kg, ip.)-stimulated salivary chloride concentration was measured. The relationship between salivary chloride concentration and mean intake of 0.15 M NaCl solution was also U shaped, with the minimal NaCl intake associated with a salivary chloride concentration of 54 meq/liter. During the second week of treatment with DOCA, all rats were offered a choice between 0.25 M NaCl solution and distilled water. Rats receiving DOCA at doses of 102.1 micrograms/day or greater had a significantly lower intake of NaCl solution than those receiving either captopril alone or 66.5 micrograms DOCA/day in combination with captopril. These results indicate that the appetite for NaCl solution induced by captopril can be inhibited by concurrent administration of DOCA. They also suggest that changes in the concentration of electrolytes in saliva may be associated with changes in the appetite for NaCl solution.

Animals↗

Loss of appetite: a poetic exploration of cancer patients' and their carers' experiences.

AIM: To explore the experience of loss of appetite among palliative care cancer patients and their carers supported by a specialist palliative care team in the community. METHOD: Semistructured interviews were conducted with seven palliative care cancer patients and their carers in the community. A poetic transcription of participants' words was made to capture and communicate the essence of each person's experience before the thematic analysis was undertaken. FINDINGS: Six common themes emerged from the data: a fickle phenomenon; the cost of caring; facing uncertainty and death; adaptations; accepting limitations; and what patients want: 'listen to me'. These were illustrated by the poetic transcriptions. CONCLUSION: Meeting the differing needs of palliative care patients with loss of appetite and their carers is challenging. It demands a thorough assessment of symptoms, an understanding of the underlying pathophysiology and of the role food plays in society. An understanding of the experience of loss of appetite is essential to the provision of appropriate care and support to those affected by it. The study demonstrated that, although unusual, poetic transcriptions can be an effective method of presenting data in terms of acceptability to participants and communicating their experience to others.

Adaptation, Psychological↗

Effect of naloxone on appetitive and consummatory phases of ethanol self-administration.

BACKGROUND: The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. METHODS: Intraperitoneal injections of naloxone (0.3-10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. RESULTS: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. CONCLUSIONS: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior.

Alcohol Drinking↗

Heterogeneity of blood pressure responses to salt restriction and salt appetite in rats.

In contrast to a widely held belief, the response of blood pressure to even marked changes of salt (NaCl) intake is extremely heterogeneous in different strains of laboratory rats. Like in healthy humans, it is rather difficult to induce an increase or a decrease of blood pressure in normotensive rats by the manipulation of dietary salt consumption within a reasonable range. Moreover, severe NaCl restriction is sometimes associated with a paradoxical rise in blood pressure. No direct relation appears to exist between salt appetite and blood pressure. We showed that salt appetite was increased after dietary NaCl restriction in normotensive Wistar rats compared with normotensive Fischer 344 rats. The latter had a high renin status which was not sensitive to changes in dietary salt. An altered peripheral or central renin metabolism in this rat strain might be partly responsible for their relative lack of salt appetite and could be related to their notable lack of blood pressure sensitivity to dietary NaCl.

Animals↗

Ostertagia ostertagi infection in the calf: effects of a trickle challenge on appetite, digestibility, rate of passage of digesta and liveweight gain.

The effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day on appetite, digestibility, rate of passage of digesta and liveweight gain were investigated in 12 calves assigned to infected, pair-fed control and ad libitum-fed control groups. Digestibility of cellulose, nitrogen, organic matter and dry matter was determined using insoluble acid detergent fibre as a marker on two occasions during the study: (i) Between days 31 and 38, when abomasal dysfunction was greatest; and (ii) between days 52 and 58, beginning approximately one week after anthelmintic treatment (day 46). Rate of passage of digesta was measured using chromium mordanted hay, fed to each calf after each digestibility study period. Voluntary feed intake of the infected group was significantly reduced from day 37 with the greatest depression (77 per cent) occurring just before anthelmintic treatment. The drop in appetite was responsible for nearly 73 per cent of the difference in liveweight gain between the infected and ad libitum fed control groups. The apparent digestibility coefficient of nitrogen was significantly depressed (22 per cent) in the infected group though was restored to control levels by anthelmintic treatment. The rate of passage of digesta was significantly reduced in both pair-fed control (50 per cent) and infected (74 per cent) groups. Anthelmintic treatment increased the latter though only to pair-fed control group levels. It is suggested that the marked hypergastrinaemia seen in the infected calves may have been in part responsible for the decreased rate of passage of digesta and in turn for the drop in appetite.

Animals↗

A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.

PURPOSE: To evaluate the appetite-stimulating properties of delta-9-tetrahydrocannabinol (THC) in patients with anorexia due to advanced cancer. PATIENTS AND METHODS: Nineteen patients with various malignancies were entered. All had cancer-associated anorexia and a life expectancy greater than four weeks. Patients were started on THC 2.5 mg p.o. t.i.d. one hour after meals for four weeks. Evaluations for side effects, efficacy, acceptability and satisfaction were conducted at two and four weeks. RESULTS: 18 patients were evaluable. Ten patients completed the entire 28-day study. Four patients experienced grade I toxicity and three withdrew at their request. Thirteen patients reported an improved appetite. CONCLUSION: THC is an effective appetite stimulant in patients with advanced cancer. It is well tolerated at low doses. Further studies are needed to determine the most appropriate dose and the specific population most likely to respond.

Administration, Oral↗

Acute effects of a single exercise class on appetite, energy intake and mood. Is there a time of day effect?

This study aimed to investigate the acute effects of a single exercise class on appetite sensations, energy intake and mood, and to determine if there was a time of day effect. Twelve healthy, young, normal weight females, who were non-regular exercisers, participated in four trials: morning control, morning exercise, evening control and evening exercise. Exercise trials were a one-hour class of aerobic and muscle conditioning exercise of varying intensities, to music. Control trials were a one-hour rest. Ratings of perceived exertion were significantly greater during the warm-up and muscle conditioning parts of the morning exercise trial compared to those of the evening exercise trial. Although both exercise trials, compared to control trials, produced an increase in appetite sensations, they did not alter energy intake and produced a decrease in 'relative' energy intake. In relation to mood, both exercise trials increased positive affect and decreased negative affect. These results suggest that a single exercise class, representative of that offered by many sports centres, regardless of whether it is performed in the morning or evening produces a short-term negative energy balance and improves mood in normal weight women. However, when this type of exercise was performed in the morning it was perceived to require more effort.

Adolescent↗

Immunohistochemical and genomic evidence for the involvement of hypothalamic neuropeptide Y (NPY) in phenylpropranolamine-mediated appetite suppression.

Phenylpropanolamine (PPA) is an appetite suppressant. The mechanism for the anorectic effect of PPA has been attributed to its action on the site of hypothalamic paraventriculum. Neuropeptide Y (NPY) is an appetite stimulant that is widely distributed in the site of hypothalamus. It is not clear whether hypothalamic NPY is involved in the anorectic action of PPA. This study was aimed to investigate the mechanism underlying the involvement of NPY gene in the anorectic action of PPA. Results revealed that PPA treatment in rats could decrease both NPY content and mRNA level in the hypothalamus. In addition, the expression of NPY immunoreactivity following PPA treatment was decreased in areas of hypothalamic arcuate nucleus, paraventricular nucleus and periventricular area using immunohistochemical staining, suggesting an involvement of NPYergic pathway in the action of PPA anorexia. Our results provided immunohistochemical and genomic evidence to suggest that PPA might reduce feeding by altering NPY gene expression.

Animals↗

Down-regulation of cannabinoid-1 (CB-1) receptors in specific extrahypothalamic regions of rats with dietary obesity: a role for endogenous cannabinoids in driving appetite for palatable food?

Agonists at cannabinoid-1 (CB-1) receptors stimulate feeding and particularly enhance the reward aspects of eating. To investigate whether endogenous cannabinoids might influence appetite for palatable food, we compared CB-1 receptor density in the forebrain and hypothalamus, between rats fed standard chow (n=8) and others given palatable food (n=8) for 10 weeks to induce dietary obesity. CB-1 receptor density was significantly decreased by 30-50% (P<0.05) in the hippocampus, cortex, nucleus accumbens and entopeduncular nucleus of diet-fed rats. Furthermore, CB-1 receptor density in the hippocampus, nucleus accumbens and entopeduncular nucleus was significantly inversely correlated with intake of palatable food (r(2)=0.25-0.35; all P<0.05). By contrast, CB-1 receptor binding in the hypothalamus was low and not altered in diet-fed rats. CB-1 receptor down-regulation is consistent with increased activation of these receptors by endogenous cannabinoids. Acting in areas such as the nucleus accumbens and hippocampus, which are involved in the hedonic aspects of eating, cannabinoids may therefore drive appetite for palatable food and thus determine total energy intake and the severity of diet-induced obesity. However, cannabinoids in the hypothalamus do not appear to influence this aspect of eating behaviour.

Animals↗

Eating habits and appetite control in the elderly: the anorexia of aging.

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.

Aged↗

The soybean beta-conglycinin beta 51-63 fragment suppresses appetite by stimulating cholecystokinin release in rats.

We previously demonstrated that soybean beta-conglycinin peptone suppresses food intake and gastric emptying by direct action on rat small intestinal mucosal cells to stimulate cholecystokinin (CCK) release. The aim of the present study was to define the active fragment in beta-conglycinin by using synthetic peptides chosen from the sequence of three beta-conglycinin subunits. We selected the fragments that had multiple nonadjacent arginine residues, and investigated their ability to bind to components of the rat intestinal brush border membrane as well as to stimulate CCK release and appetite suppression. The fragment from 51 to 63 of the beta subunit (beta 51-63) had the strongest binding activity. Intraduodenal infusion of beta 51-63 inhibited food intake and markedly increased portal CCK concentration. The threshold concentration of beta 51-63 to affect food intake was 3 micro mol/L. The CCK-A receptor antagonist abolished the beta 51-63-induced suppression of food intake. Three types of smaller fragments of beta 51-63 (beta 51-59, beta 53-63 and beta 53-59) and two types of fragments similar to beta 51-63 in the beta-conglycinin alpha and alpha' subunits (alpha 212-224 and alpha' 230-240) had less binding ability than did beta 51-63. Model peptides constructed with arginine (R) and glycine (G), such as GRGRGRG, had strong binding affinity, but peptides containing a single R or RR did not. These results indicate that the beta-conglycinin beta 51-63 fragment is the bioactive appetite suppressant in beta-conglycinin, and multiple arginine residues in the fragment may be involved in this effect.

Animals↗

Effects of neuropeptide Y on appetitive and consummatory behaviors associated with alcohol drinking in wistar rats with a history of ethanol exposure.

BACKGROUND: Neuropeptide Y (NPY) reduces ethanol intake under free access conditions in Wistar rats with a history of prolonged ethanol vapor exposure. The current study was designed to determine whether NPY differentially alters ethanol-associated appetitive behavior (i.e., lever pressing) or ethanol consumption in Wistar rats with a history of ethanol vapor exposure. METHODS: Wistar rats were first trained to self-administer 10% ethanol in a paradigm that provided 25 min of free access to 10% ethanol after completing a 20-lever press response requirement (i.e., an RR20 schedule). After stable level lever pressing was established, operant sessions were suspended during a 9-week period of ethanol vapor exposure. Self-administration sessions were then reinstituted, and a fixed time (FT) schedule of 10% ethanol access was used to assess the effects of ethanol exposure and NPY on lever pressing and drinking behavior. Under the FT schedule, the maximum number of lever presses emitted within 10 min was assessed before providing access to 10% ethanol. RESULTS: Ethanol vapor exposure did not alter patterns of lever pressing under the RR20 schedule, but lever presses emitted under the FT schedule were reduced after ethanol vapor exposure. Ethanol intake was significantly increased after ethanol vapor exposure. NPY significantly reduced ethanol intake but did not significantly reduce lever pressing under the FT schedule. CONCLUSIONS: Taken together, these data suggest that chronic ethanol exposure increases ethanol intake without clearly enhancing its reinforcing value. Furthermore, NPY has a greater impact on the consummatory factors mediating ethanol intake than appetitive factors mediating ethanol seeking.

Administration, Inhalation↗

The appetite-suppressant effect of nicotine is enhanced by caffeine.

AIM: To test whether the anorectic effect of nicotine may be amplified by caffeine. METHODS: Chewing gums with nicotine and caffeine were administered to 12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a randomized, double blind, cross over design. Appetite sensations were measured using visual analogue scales. RESULTS: Hunger and prospective food consumption were negatively associated with the increasing doses of nicotine, whereas satiety and fullness were positively associated with the increasing doses of nicotine (p < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and fullness as a caffeine x nicotine x time interaction was observed in these scores (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of caffeine caused nausea in four of the non-smokers. However, the effects of nicotine and the caffeine x nicotine x time interaction persisted after the exclusion of these subjects. CONCLUSION: Caffeine added to nicotine chewing gum appears to amplify its attenuating effects on appetite and the combinations of 1-mg of nicotine with caffeine seem to be well tolerated.

Adolescent↗

Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats.

Although amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter abundant in the brain, molecular mechanisms underlying this effect are not well known. This study examined the possible role of protein kinase A (PKA) and cAMP response element-binding protein (CREB) signaling in this anorectic effect, and the results showed that both PKA and CREB mRNA levels in hypothalamus were increased following AMPH treatment, which was relevant to a reduction of NPY mRNA level. To determine whether PKA or CREB was involved in the anorectic response, intracerebroventricular infusions of antisense oligonucleotide (or missense control) were performed 60 min before daily AMPH treatment in conscious rats, and results showed that either PKA or CREB knockdown could block AMPH-induced anorexia as well as restore NPY mRNA level, indicating the respective involvement of PKA and CREB signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA and CREB signaling may involve the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.

Amphetamine↗

An approach to the development of drugs for appetite disorders.

This review covers some modern concepts in the development of drugs to treat appetite disorders. Specific attention is paid to the peripheral satiety system and the role of gastrointestinal peptides such as cholecystokinin in the pathogenesis of satiety. Alterations in neuropeptide Y and/or peptide YY are suggested to play a role in the pathophysiology of bulimia. Corticotropin-releasing factor is a putative candidate peptide involved in anorexia nervosa. The serotonin reuptake inhibitors fenfluramine and fluoxetene decrease weight in obese subjects. Endogenous opioids modulate the choice of palatable foods. Anorexia in the old appears to be related to a decrease in opioid feeding drive and an excess of the satiety action of cholecystokinin. Other agents involved in weight regulation include those which alter gastric emptying, increase thermogenesis, or modulate fat cell metabolism. It should be stressed that many neurotransmitters that modulate appetite also alter other behaviors, increasing their propensity to produce side effects.

Animals↗

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients.

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We infused GLP-1 (2.4 pmol.kg-1.min-1) or saline subcutaneously for 48 h in randomized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed energy intake and on plasma glucose, insulin, glucagon, postprandial lipidemia, blood pressure, heart rate, and basal metabolic rate. RESULTS: The infusion resulted in elevations of the plasma concentrations of intact GLP-1 similar to those observed after intravenous infusion of 1.2 pmol.kg-1.min-1, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas fullness was unaffected. No side effects during GLP-1 infusion were recorded except for a brief cutaneous reaction. Basal metabolic rate and heart rate did not change significantly during GLP-1 administration. Both systolic and diastolic blood pressure tended to be lower during the GLP-1 infusion. CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.

Adult↗