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Behavior, appetite, and urinary cortisol responses by adult female pigtailed macaques to cage size, cage level, room change, and ketamine sedation.

Pigtailed macaques (Macaca nemestrina) and longtailed macaques (M. fascicularis) show behavioral, ecological, and possible temperament differences, and their responses to the laboratory environment might therefore be quite different. We tested pigtailed macaques under the same conditions that were investigated in a previous study with longtailed macaques, using the same comprehensive set of physiological and behavioral measures of stress. First, eight adult females' adaptation to a new room in regulation-size cages was monitored, and in the third week their responses to ketamine sedation were measured. Then they spent two weeks singly housed in each of four cage sizes (USDA regulation size, one size larger, one size smaller, and a very small cage). Half of the subjects were in upper-level cages and the remainder in lower-level cages for the entire study. Cage size, ranging from 20% to 148% of USDA regulation floor area, was not significantly related to abnormal behavior, self-grooming, manipulating the environment, eating/drinking, activity cycle, cortisol excretion, or biscuit consumption. Locomotion and frequency of behavior change were significantly reduced in the smallest cage, but did not differ in cage sizes ranging from 77% to 148% of regulation size. The only manipulation to produce an unequivocal stress response, as measured by cortisol elevation and appetite suppression, was ketamine sedation. Room change and cage changes were associated with minimal cortisol elevation and appetite suppression. Wild-born females showed more appetite suppression after room change than captive-born females. No differences were related to cage level. Pigtailed macaques strongly resembled longtailed macaques except they showed weaker responses to the new room and cage change, probably because the pigtails had spent more time in captivity. These findings support the conclusion that increasing cage size to the next regulation size category would not have measurable positive effects on the psychological well-being of two species of laboratory macaques.

Anesthetics, Dissociative↗

Role of leptin in regulating appetite, neuroendocrine function, and bone remodeling.

Leptin, a hormone secreted by adipocytes, acts on the hypothalamus to regulate appetite and neuroendocrine function. In the hypothalamus, both the arcuate nucleus and the ventromedial nucleus express leptin receptors. Specific neurons in the arcuate nucleus regulate appetite and reproduction. In contrast, neurons in the ventromedial nucleus regulate bone mass. The melanocortin system is the downstream pathway for regulating appetite and neuroendocrine function. In contrast, the sympathetic nervous system is the downstream pathway for regulating bone mass. Leptin, in regulating food intake and body weight, acts, in part, by inhibiting the synthesis of neuropeptide Y and its release from the hypothalamus. The leptin and insulin pathways may interact and may be important in the pathogenesis of the metabolic syndrome.

Animals↗

Parabrachial nuclei damage in infant rats produces residual deficits in gustatory preferences/aversions and sodium appetite.

Ten-day-old rats sustained bilateral electrolytic lesions of the parabrachial nuclei in the pons (PBN). Growth measures and tests of sensorimotor, feeding and drinking behaviors, sodium appetite, and gustatory capacities were made between ages 1 and 150 days. PBN rats displayed a transient period of attenuated suckling, as evidenced by body weight loss. When tested soon after weaning, PBN rats were hyperdipsic in response to cellular dehydration and during food deprivation. This effect, however, was temporary. When tested as adults, PBN rats were hypodipsic in response to extracellular fluid volume depletion, they displayed alterations in sodium appetite, showed "exaggerated" preferences and aversions to saccharin and NaCl solutions, and they displayed attenuated quinine aversions. These results are generally similar to the behaviors of rats sustaining more central gustatory pathway lesions as adults. The functional significance of the PBN in the developing rat for preference/aversion and sodium appetite behaviors are discussed.

Animals↗

Changes in the categorization of appetitive and aversive events during postnatal development of the rat.

Environmental stimuli are not clearly categorized into appetitive and aversive classes during the first postnatal week. Three- and 6-day-old rats are highly activated by nominally appetitive (milk infusions) and aversive (foot shock) stimuli. Both evoked the same generalized behavioral responses (rolling, curling). By 12 days of age, these stimuli were responded to differently; mouthing and probing occurred in response to milk while flinching and escape responses were observed to shock. The affective properties of mild shock were found to be hedonically opposite for 6- and 12-day-old pups. Six-day-olds showed an acquired preference for an odor paired with shock which increased with intensity (.1-.5 mA) similar to that observed with milk infusions. An acquired odor aversion was displayed by 12 days old using these shock parameters. These results suggest that young rat pups may not differentiate many appetitive and aversive events behaviorally or affectively until the second postnatal week.

Affect↗

Acquisition of an appetitive behavior prevents development of stress-induced neurochemical modifications in rat nucleus accumbens.

In rats, exposure to chronic unavoidable stress produces a decrease in dopamine output in the nucleus accumbens shell that is accompanied by a decreased density of the dopamine transporter and an increased activity of the dopamine-D(1) receptor complex. These modifications have been hypothesized to be adaptive to decreased dopamine output in stressed rats. We investigated whether the learning of an appetitive behavior sustained by palatable food, which is associated with increased dopamine output in the nucleus accumbens shell as measured by microdialysis experiments, would affect the modifications induced by chronic stress exposure on dopamine transporter density and dopamine-D(1) receptor complex activity in the nucleus accumbens. Rats exposed to chronic unavoidable stress after acquisition of the appetitive behavior showed a higher dopamine extraneuronal release in the nucleus accumbens shell than that of stressed animals, and similar to that of control rats. Moreover, previous acquisition of the appetitive behavior prevented development of a stress-induced decrease in dopamine transporter density, measured by [(3)H]-WIN 35428 binding, a stress-induced increase in dopamine-D(1) receptor density, measured by binding of [(3)H]-SCH 23390, and SKF 38393-stimulated adenylyl cyclase activity in the nucleus accumbens. These results support the hypothesis that changes induced in pre- and postsynaptic dopaminergic transmission by chronic stress exposure are related to decreased dopamine output.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Nicotinic receptor-mediated effects on appetite and food intake.

It is well known, although not well understood, that smoking and eating just do not go together. Smoking is associated with decreased food intake and lower body weight. Nicotine, administered either by smoking or by smokeless routes, is considered the major appetite-suppressing component of tobacco. Perhaps the most renowned example of nicotine's influence on appetite and feeding behavior is the significant weight gain associated with smoking cessation. This article presents an overview of the literature at, or near, the interface of nicotinic receptors and appetite regulation. We first consider some of the possible sites of nicotine's action along the complex network of neural and non-neural regulators of feeding. We then present the hypothesis that the lateral hypothalamus is a particularly important locus of the anorectic effects of nicotine. Finally, we discuss the potential role of endogenous cholinergic systems in motivational feeding, focusing on cholinergic pathways in the lateral hypothalamus.

Animals↗

Cyproheptadine is an effective appetite stimulant in cystic fibrosis.

Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF). Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis. We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF. This was a 12-week, randomized, double-blind, controlled trial of CH vs. placebo. Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study. Subjects were seen at baseline and every 4 weeks. Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey. Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs. 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass. There were no changes or differences in PO or IV antibiotic use or spirometric changes. No significant side effects except transient mild sedation occurred in the CH group. Patient acceptance was good. In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF.

Adolescent↗

Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis.

Appetite stimulants have been used to help overcome decreased appetite and malnutrition in children and adults with various chronic illnesses, including cystic fibrosis (CF). Stimulants have included megestrol acetate (MA), cyproheptadine hydrochloride (CH), cannabinoids, hydrazine sulfate, anabolic hormones, and growth hormone. Many of these, including MA, have substantial side effects and may not be suitable for prolonged use. We previously studied the effects of CH on weight gain in a short-term (12 week) trial in CF with good results compared to placebo. Side effects were few, and weight gain was significant. In this study, we sought to determine the effects of CH over a longer term in order to assess its suitability for prolonged use. Sixteen CF children and adults enrolled in the original short-term study subsequently entered this study, and 12 completed the 9-month trial. All patients receiving placebo in the original short-term study received CH 4 mg up to four times a day in the long-term study continuation, and those receiving CH in the short-term study continued on the drug. No pill counts were done, and patients were queried at quarterly visits as to their CH use. Anthropometrics and spirometry were also done quarterly, and antibiotic use was quantified. Subjects who had changed from placebo (CH2 group) gained weight significantly over 3-6 months, and those continuing on CH (CH1 group) generally maintained previously gained weight over the duration of the study. Select spirometric measures improved in both groups but not significantly, and side effects were mild. CH appears to be an effective appetite stimulant in CF, and generally maintains its effect over time with an acceptable side-effect profile.

Adolescent↗

Effects of intragastric infusions of fat and carbohydrate on appetite ratings and food intake from a test meal.

Previous studies using meal preloads have indicated that carbohydrate has a greater satiating power than fat. To investigate the effects of macronutrients on ingestion and satiety, without the influence of meal design and orosensory factors, two groups of ten healthy, fasted male volunteers took part in two separate experiments involving rapid direct intragastric infusions of macronutrients. In the first experiment volunteers received isocaloric infusions of either Intralipid, or 1:1 Intralipid and glucose mixture or saline over 15 min on three separate occasions. In a second experiment volunteers received isocaloric infusions of either Intralipid or glucose. For both studies, appetite ratings were recorded for the first two hours of the study and energy and macronutrient intakes were evaluated from a test meal given 1.5 h after the infusion. Food diaries were used to monitor food intake for the remainder of the study day. In the first experiment, both Intralipid and the Intralipid/glucose mixture suppressed appetite ratings and reduced energy intake at lunch compared with saline but had no effect on energy intake during the remainder of the study day. No differences were found between nutrient conditions in suppressing appetite ratings or energy intake. In the second experiment there were no differences between the effects of Intralipid and glucose on hunger, fullness or on energy intake from the test meal or intake over the remainder of the day. Taken together, these results suggest that intragastric infusions of either Intralipid, glucose or a mixture of the two, reduced hunger and increased fullness, but they failed to confirm the hypothesis that different macronutrients have different satiating capacities.

Adolescent↗

Effect of contingent hunger state on development of appetite for a novel fruit snack.

Eating more fruit can reduce risk of cancer and cardiovascular disease. Understanding barriers to this behaviour is critical for strategies to encourage it. We addressed the question whether the level of hunger at which fruit is eaten would influence the development of appetite for fruit. Half the participants were asked to eat a pair of novel fruit snacks (dried fruit bar; 50 kcal each) exclusively when hungry (at least 3 hours since last eating), and half to eat them exclusively when full (20-30 minutes after a meal), twice a day for one week. Rated appetite for the bars, and ad-libitum intake, were measured when hungry and full, on 2 days prior to, and 2 days after this week. Compliance was assessed from dietary diaries. Thirty participants (22 women, 8 men) completed the study satisfactorily. For the group eating the fruit bars only when hungry (hungry-trained), intake increased after the week, but only when full at the time of testing. Other measures of appetite for this group were unaffected, with the exception of a reduced desire to eat the bars when tested hungry. Ranked preference for the trained flavour increased exclusively among hungry-trained subjects, but only for those who had reported their preferred snack food to be fruit. No change in any measure was found for the group eating the fruit bars exclusively when full. The results suggest the hungry-trained group learnt that the bars lacked strong satiation, thus allowing greater intake when full (learnt desatiation). For the same reason, however, the prospect of eating the bars when mildly hungry lost its appeal. Eating fruit between meals may not encourage snacking on fruit, unless hunger is absent at the time of consumption.

Adolescent↗

Effect of sucrose and safflower oil preloads on short term appetite and food intake of young men.

The effects of carbohydrate and fat on satiety have been examined primarily through meal composition studies. The purpose of this study was to compare the effects of pure sucrose and safflower oil, isovolumetric beverage preloads, on appetite (measured every 15 minutes by visual analogue scales) and food intake 60 minutes later. Young men consumed 0, 418, 836 and 1254 kJ of sucrose in the first two experiments and these same doses of safflower oil in the third. Finally, the largest doses of sucrose and safflower oil were compared. Sucrose, but not safflower oil, suppressed average appetite compared with control. In experiment 2, food intake was reduced (p<0.05) by 518 kJ after the 418 and 836 kJ preloads and by 1129 kJ after the 1254 kJ sucrose preload. Only the 1254 kJ dose of safflower oil significantly suppressed food intake by 480 kJ in the third experiment. When the 1254 kJ doses were compared directly, sucrose suppressed food intake by 653 kJ compared with control where as safflower oil did not. It is concluded that, in the short-term, sucrose produces a dose dependent reduction in appetite and food intake that is greater than that produced by safflower oil.

Adult↗

Magnesium appetite in the rat.

Rats modify their ingestive behaviour to correct deficiencies of minerals such as sodium and calcium. Here, we examined the effect of magnesium deprivation on the ingestion of MgCl2 and other solutions. Male Sprague-Dawley rats were fed a nutritionally complete or magnesium-deficient diet and were then given 3.2, 10, 32, or 100mM MgCl2, 32mM CaCl2, 32mM NaCl, 10mM HCl, or 2.5mM saccharin, and their intake was measured for 24h in a two-bottle choice test with water. Within the first 5 min, magnesium-deprived subjects given 3.2, 32, or 100mM MgCl2 or 32mM CaCl2 drank significantly more of these solutions than did replete rats. In a separate study, rats fed replete, magnesium-deficient, or calcium-deficient diets were given a three-bottle choice between water, 32mM MgCl2, and 32mM CaCl2. The deprived rats preferred the solution that ameliorated their deficiency; for example, during the first 1h, the magnesium-deprived rats drank 3.1 +/- 0.5ml MgCl2 and 1.1 +/- 0.4ml CaCl2, whereas the calcium-deprived rats drank 1.8 +/- 0.5ml MgCl2 and 3.9 +/- 0.4ml CaCl2. Thus, magnesium deprivation leads to a compensatory appetite for magnesium, and the appetites for magnesium and calcium are distinct and specific. The rapid expression of magnesium appetite suggests that it depends in part on innate, gustatory factors.

Analysis of Variance↗

The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration.

This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of hypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin and serotonin are additional candidate neurochemicals with postulated inhibitory central actions and with essential roles in the overall integration of sensory input within the neural network devoted to maintaining hydromineral balance.

Appetite↗

Inhibitory avoidance and appetitive learning in aged normal mice: comparison with transgenic mice having elevated plasma growth hormone levels.

Groups of 25-month-old ("old") B6C3 hybrid male mice, 6-month-old ("young") normal males, and their age-matched transgenic (TG) siblings overexpressing the bovine growth hormone gene were given an inhibitory avoidance training trial (0.20-mA electric shock, 1.0-s duration). The old B6C3 hybrids and the young TG mice displayed poorer retention (shorter latencies to enter the shock compartment) 24 h and 42 days after training than did the young normal mice. In a subsequent multiple-trial acquisition test, young TG and old normal mice required more trials to reach the criterion of complete inhibition of step-through responding for 300 s than did young normal mice. Young normal and young TG mice did not differ in trials to extinction, but TG mice met the extinction criterion sooner than did old normal mice, suggesting poorer longterm retention. In tests of T-maze appetitive learning, young normal, old normal, and young TG mice did not differ in acquisition or 24-h retention. Contrary to expectation, TG mice acquired T-maze reversal learning in fewer trials than did young normal or old normal mice. The TG and young normal mice did not differ in retention when retested 44 days after initial training, but old normal mice showed poorer retention than did the young normals. Results of locomotor activity and shock response tests suggested that learning impairments were not due to differences in locomotor activity or shock response thresholds in these animals. Tests in an elevated plus maze indicated that young TG mice were less anxious in a novel environment than their normal siblings, which may contribute to their impaired inhibitory avoidance learning. These findings suggest that 6-month-old TG mice overexpressing the bovine growth hormone gene display alterations in inhibitory avoidance (but not appetitive) learning similar to those occurring in 25-month-old normal mice. The neurobiological mechanisms mediating inhibitory avoidance and T-maze appetitive learning in these animals may be largely dissociated.

Aging↗

Hormonal regulation of appetite and body mass in patients with advanced prostate cancer treated with combined androgen blockade.

Cachexia is rarely observed in patients with advanced prostate cancer treated with combined androgen blockade. Androgens play an important role in the regulation of body mass composition and influence the secretion of leptin, the appetite regulating hormone. The aim of the study was to assess the influence of a combined treatment with nonsteroidal antiandrogen and LH-RH analogue on the hormonal regulation of appetite and changes in body mass in patients with advanced prostate cancer (Whitmore-Jewett stage D1 or D2). Eighteen patients with prostate cancer and 17 healthy subjects matched for age and body mass index were included. In all patients serum concentrations of leptin, neuropeptide Y (NPY), insulin, testosterone and estradiol were measured before and after four and twelve weeks of androgen blockade. Pretreatment serum leptin levels were similar in patients with prostate cancer and in the controls. In a multiple regression analysis only body mass index and testosterone significantly contributed to the variation of plasma leptin. During the treatment body mass and plasma leptin significantly increased while NPY decreased. The change of plasma NPY was significant only after 4 weeks of therapy. This study shows that the afferent regulation of leptin secretion is unchanged in advanced prostate cancer. Androgen ablation significantly increases body mass and influences secretion of appetite regulating hormones. Testosterone appears to play a significant role in the regulation of leptin secretion.

Adenocarcinoma↗

Dopamine antagonists alter response allocation but do not suppress appetite for food in rats: contrast between the effects of SKF 83566, raclopride, and fenfluramine on a concurrent choice task.

RATIONALE: Dopamine is important for enabling organisms to overcome work-related response costs. One way of investigating this function has been with concurrent choice procedures using food reinforcement. In the present study, rats were given a choice between pressing a lever for preferred Bioserve pellets, or approaching and consuming a less-preferred laboratory chow that was concurrently available. In previous work with this task, dopamine antagonists and accumbens dopamine depletions decreased lever pressing but increased chow consumption. OBJECTIVE: The present study assessed three drugs (two dopamine antagonists and one appetite suppressant) using the lever pressing/chow feeding task. RESULTS: Under baseline conditions, rats pressed the lever at high rates (1,300-1,500 responses) to obtain the preferred food, and little of the laboratory chow was eaten (1-2 g). Selective D1 and D2 antagonists (SKF 83566 and raclopride) reduced fixed ratio 5 lever pressing, but substantially increased chow consumption. In contrast, the serotonergic appetite suppressant fenfluramine reduced both lever pressing and chow consumption. With the dopamine antagonists, lever pressing and chow consumption were inversely correlated across treatments, while these two measures were unrelated in the fenfluramine experiment. CONCLUSIONS: Dopamine antagonists and accumbens dopamine depletions do not simply reduce appetite. Rats with accumbens dopamine depletions, or rats treated with low doses of selective or non-selective dopamine antagonists, remain directed toward the acquisition and consumption of food. These results demonstrate that fundamental aspects of food reinforcement are left intact after treatment with low doses of dopamine antagonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Imipramine restores the long-term impairment of appetitive behavior in socially stressed rats.

RATIONALE: Previous observations revealed that defeated and subsequently individually housed rats do not display behavioral anticipatory responses to the conditioned presentation of a bell/light stimulus associated with free access to a 5% sucrose solution reward. The absence of the appetitive responses suggests a decreased sensitivity to reward. This might be homologous to anhedonia, a symptom of human depression. OBJECTIVES: To further validate the inability to anticipate as indicative for a depressionlike state we investigated whether antidepressant treatment restores the impaired anticipatory responses in defeated and subsequently individually housed animals. METHODS: Male rats were defeated and subsequently individually housed or subjected to a control treatment. In the 19-20th weeks after the exposure to defeat rats were either injected daily with imipramine (20 mg/kg per os, dissolved in water) or water. Anticipatory behavior was measured both before and after 3-5 weeks of chronic treatment with imipramine. RESULTS: The long-term impairment of anticipatory behavior in defeated and subsequently individually housed rats was restored by chronic imipramine treatment. Impaired appetitive behavior in socially stressed rats was not accompanied by a decreased consumption of the 5% sucrose solution in the anticipatory tests. The recovery of the appetitive responses was independent of open field activity, body weight, and 5% sucrose preference in the home cage. CONCLUSIONS: Chronic imipramine administration restores the anhedonialike absence of anticipatory behavior in socially stressed rats. Predictive validity of the social stress model of human depression is suggested by the similar action of imipramine on the modeled behavior and on the anhedonia symptoms in depressive human patients.

Animals↗

Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite.

Conjugated linoleic acid (CLA) has been demonstrated to reduce body fat in animals. However, the mechanism by which this reduction occurs is unknown. Leptin may mediate the effect of CLA to decrease body fat. We assessed the effects of 64 d of CLA supplementation (3 g/d) on circulating leptin, insulin, glucose, and lactate concentrations in healthy women. Appetite was assessed as a physiological correlate of changes in circulating leptin levels. Analysis of plasma leptin concentrations adjusted for adiposity by using fat mass as a covariate showed that CLA supplementation significantly decreased circulating leptin concentrations in the absence of any changes of fat mass. Mean leptin levels decreased over the first 7 wk and then returned to baseline levels over the last 2 wk of the study in the CLA-treated group. Appetite parameters measured at around the time when the greatest decreases in leptin levels were observed showed no significant differences between supplementation and baseline determinations in the CLA-supplemented group or between the CLA and placebo-supplemented groups. There was a nonsignificant trend for mean insulin levels to increase toward the end of the supplementation period in CLA-treated subjects. CLA did not affect plasma glucose and lactate over the treatment period. Thus, 64 d of CLA supplementation in women produced a transient decrease in leptin levels but did not alter appetite. CLA did not affect these parameters in a manner that promoted decreases of adiposity.

Adipose Tissue↗