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Effects of inedible, manipulable objects on captive bears.

Bears in captivity often show abnormal behaviors such as stereotypies and periods of excessive inactivity. Most of the research aimed at reducing abnormal behaviors in bears has focused on feeding enrichment. However, the effects of feeding enrichment only seem to last as long as it takes a bear to consume the food. This study investigated the effects of inedible, manipulable objects on bears. Two polar bears (Ursus maritimus) received plastic floats. A sloth bear (Melursus ursinus) and a spectacled bear (Treniarctos ornatus) received plastic balls. During a 7-week period, polar bears nearly doubled their activity in the presence of toy floats, and the spectacled bear halved its pacing in the presence of toys. The sloth bear did not respond to the objects. These findings indicate that access to manipulable nonfood objects such as plastic toys can result in prolonged engagement in appetitive behaviors by polar bears.

Journal Article↗

Association between the insulin-like growth factor 2 gene (IGF2) and scores on the Eating Attitudes Test in nonclinical subjects: a family-based study.

OBJECTIVE: An interesting candidate gene for eating disorders is the gene for insulin-like growth factor 2 (IGF2). Located on chromosome 11p15.5, IGF2 is a member of the insulin family of polypeptide growth factors that is involved in development and growth. Consistent with its profile of metabolic actions, an association has been reported between a single nucleotide polymorphism (SNP) in the 3' untranslated region of the IGF2 gene (ApaI) and body mass index. This investigation extended these studies and investigated the psychological and behavioral implications of this hormone's impact on metabolism and body composition. METHOD: The authors tested nonclinical subjects from 376 families for three IGF2 SNPs and for eating disorders, as reflected in scores on the 26-item Eating Attitudes Test, a self-report questionnaire widely used as a screening instrument. RESULTS: A highly significant association was observed between the IGF2 ApaI G allele and scores on the Eating Attitudes Test overall and each of its subscales (bulimia, dieting, and oral control). Additionally, a significant association was observed between this polymorphism and body mass index. CONCLUSIONS: The current finding that the IGF2 ApaI G polymorphism, which predisposes to weight gain, may also contribute to the pathology of eating disorders is intriguing. Neurotransmitter modulation of appetitive behavior is the focus of most hypotheses regarding the etiology of severe eating disorders. The current results to some measure challenge this view, and inborn metabolic tendencies to weight gain in some women may trigger constant dieting, which in predisposed individuals eventually leads to severe eating disorders.

Adolescent↗

Cannabinoid receptor antagonists and obesity.

The cannabinoid-1 (CB1) receptor plays a role in the regulation of appetitive behavior. Exogenously administered cannabinoid receptor agonists stimulate food consumption in animals and humans. Endogenous cannabinoid receptor agonists are present in the brain, and the brain level of these agonists increases with greater demand of food by rodents. Specific CB1 receptor antagonist compounds have been discovered that display high affinity and selectivity for the CB1 receptor. CB1 receptor antagonists inhibit both acute and long-term food intake in rodents. Chronic treatment with CB1 antagonists results in a sustained reduction in body weight in rodents (5 weeks), and weight loss in humans (16 weeks). Patent literature indicates CB1 receptor antagonist discovery efforts at a number of pharmaceutical companies. The CB1 receptor antagonist, rimonabant (SR-141716), discovered by Sanofi-Synthélabo, is in phase III clinical trials for the treatment of obesity and has been found to decrease appetite and body weight in humans.

Anti-Obesity Agents↗

Efficacy of an Hypericum perforatum (St. John's wort) extract in preventing and reverting a condition of escape deficit in rats.

The treatment of unselected depressed patients with an hydro-alcoholic extract of Hypericum perforatum has been reported to have an efficacy similar to that of classical antidepressants. In the present report, the effects of H. perforatum were studied on three animal models of depression: (i) an acute form of escape deficit (ED) induced by an unavoidable stress; (ii) a chronic model of ED, which can be maintained by the administration of mild stressors on alternate days; (iii) a model of anhedonia based on the finding that repeated stressors prevent the development of an appetitive behavior induced by vanilla sugar in satiated rats fed ad libitum. H. perforatum acutely protected animals from the sequelae of unavoidable stress; such an effect was partially prevented by the administration of SCH 23390 or (-)-pindolol. Moreover, H. perforatum reverted the ED maintained by repeated stressors and preserved the animal's capacity to learn to operate for earning a positive reinforcer. It was concluded that H. perforatum contains some active principle(s) endowed with antidepressant activity.

Acute Disease↗

Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli.

Following damage to ventromedial frontal cortices, adults with previously normal personalities develop defects in decision-making and planning that are especially revealed in an abnormal social conduct. The defect repeatedly leads to negative personal consequences. The physiopathology of this disorder is an enigma. We propose that the defect is due to an inability to activate somatic states linked to punishment and reward, that were previously experienced in association with specific social situations, and that must be reactivated in connection with anticipated outcomes of response options. During the processing that follows the perception of a social event, the experience of certain anticipated outcomes of response options would be marked by the reactivation of an appropriate somatic state. Failure to reactivate pertinent somatic markers would deprive the individual of an automatic device to signal ultimately deleterious consequences relative to responses that might nevertheless bring immediate reward (or, alternatively, signal ultimately advantageous outcomes relative to responses that might bring immediate pain). As an example, activation of somatic markers would (1) force attention to future negative consequences, permitting conscious suppression of the responses leading to them and deliberate selection of biologically advantageous responses, and (2) trigger non-conscious inhibition of response states by engagement of subcortical neurotransmitter systems linked to appetitive behaviors. An investigation of this theory in patients with frontal damage reveals that their autonomic responses to socially meaningful stimuli are indeed abnormal, suggesting that such stimuli fail to activate somatic states at the most basic level. On the contrary, elementary unconditioned stimuli (e.g. a loud noise) produce normal autonomic responses.

Adult↗

The gut and food intake: an update for surgeons.

Food intake is the simplest and most obvious measure of gastrointestinal function, yet it rarely receives more than cursory attention from surgeons. In this review we cover recent findings on relationships between gut function and appetite regulation mediated via neuropeptides influenced by afferent and efferent vagal activity. Evidence from the new discipline known as neurogastroenterology elucidates gastric and intestinal signals involved in the elicitation of hunger, satiety, and aversion. Discovery of the adipose-tissue-derived hormone, leptin, has energized the field of metabolism spawning increasing numbers of publications related to interactions between leptin and insulin release and glucose disposal, as well as appetitive behavior. Peptides such as cholecystokinin (CCK), the proglucagon-derived peptides, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), and the recently identified powerful intake-stimulating molecule, orexin, are examples of potential targets for drug development and studies of surgical pathophysiology. A major conclusion of this work is that the considerable redundancy and overlap between mediators of caloric intake subserving survival of the species, while beneficial after foregut surgery, contribute to the complexity of treating the global epidemic of obesity. Possibly knowledge derived from basic research in neurogastroenterology can translate into advances in surgical treatment of obesity.

Appetite Regulation↗

Safety of Aquaflor (florfenicol, 50% type A medicated article), administered in feed to channel catfish, Ictalurus punctatus.

Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

Animal Feed↗

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

BACKGROUND: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. METHODS: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. RESULTS: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. CONCLUSIONS: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Alcohol Drinking↗

Use of leucotomy for intractable anorexia nervosa: a long-term follow-up study.

OBJECTIVE: We studied the long-term outcomes of intractable anorexia nervosa treated with leukotomy and specialized psychotherapy over 20 years ago. METHOD: All traceable subjects were interviewed using the Eating Disorders Examination (EDE) and the Structured Clinical Interview for DSM-III-R (SCID). They also completed questionnaires. Detailed histories were taken. RESULTS: Four of five female subjects were traced. Their cases had been severe, with failure of previous intensive psychotherapy and now with high risk of death from terminal inanition. One patient had committed suicide, whereas the others enjoyed a reasonable quality of life. Persistent core psychopathology was evident, but patients had not succumbed to weight loss. All suffered depression and anxiety-related disorders, but endorsed their treatment, which had allowed sustained weight gain by release of appetitive behavior, provision of a license to change, and alleviation of phobic anxiety, allowing psychotherapeutic engagement. DISCUSSION: We argue that these outcomes are relatively favorable and would not have been possible without this latter engagement in specialist psychotherapy to address burgeoning panic at unavoidable weight gain.

Adult↗

Obsessive-compulsiveness in obese weight-loss patients and normal weight adults.

It recently has been suggested that obsessive-compulsive personality characteristics may predispose people to become obese. In addition, it has been suggested that dieting may increase the frequency of thoughts about food and its consumption. The present study compared a group of 50 obese weight-loss patients to 50 normal weight adults on personality-related O-C characteristics and food and eating-related cognitions. Results supported the notion that obese weight-loss patients tend to be obsessed with food. There was no evidence that traditional O-C personality measures are related to obesity. These results suggest that effortful inhibition of appetitive behaviors may have adverse cognitive consequences.

Adult↗

The coming of genetics in the control of ingestion.

The study of appetitive behavior in relation to obesity is now being enriched by molecular-genetic findings in experimental animals with genetic obesity and associated "feeding disorders". The opinion is expressed that the mutual enrichment of the disciplines of behavior and molecular biology will place the study of human ingestive behavior on a firm scientific base.

Eating↗

Linkage disequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls.

Because of its central role in the neuromodulation of appetitive behaviors, the D2 dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to additive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, we have assayed four DRD2 RFLPs that span coding regions as well as a 3' flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism.

Adult↗

Serotonin uptake blockers and the treatment of alcoholism.

There is growing research and clinical interest in the role of brain serotonin in regulating alcohol consumption, based on two lines of evidence: negative correlations between brain serotonin levels and spontaneous alcohol consumption in rodents, and decreased alcohol intake produced by drug-induced increases in brain serotonin activity in rodents and humans. Specific blockers of neuronal serotonin uptake, such as citalopram, fluoxetine, and zimelidine, are the major drugs used in such studies. More than a dozen studies have consistently found that such specific serotonin uptake blockers reduce alcohol preference and intake in rodents, whereas nonspecific monoamine uptake blockers (e.g., amitriptyline, doxepin) do not. The effect begins within 1 hr of administration, wears off within several days of stopping drug, and often shows tolerance after 4-10 days of daily administration (the opposite time course from antidepressant action in humans). In four human, double-blind, placebo-controlled studies, citalopram (40 mg but not 20 mg daily), fluoxetine (80 mg daily), and zimelidine (200 mg more than 300 mg daily) significantly reduced alcohol intake 10-26% in social drinkers, early problem drinkers, and chronic alcoholics. The effect occurred within a few days, wore off within several days of stopping drug, and lasted throughout the 2-4 weeks of drug administration, except that in the fluoxetine study with chronic alcoholics the effect was significant only during the first week. The reduced alcohol intake was not due to sedation, antidepression, or antianxiety effects, or an aversive drug-alcohol interaction, but could be explained in part by decreased appetitive behavior (two studies found that subjects lost weight) or a conditioned (taste) aversion to alcohol promoted by serotonin (as occurs in animals). Further research is also needed to clarify the neuropharmacological mechanism of action, since the alcohol intake-reducing effects in rodents are not blocked by serotonin receptor antagonists or brain serotonin depletion. Regardless of mechanism, serotonin uptake blockers offer a potentially promising new treatment for alcoholism.

Alcohol Drinking↗

Reward anticipation, cognition, and electrodermal activity in the conditioned monkey.

In the present report, we examine electrodermal activity (skin conductance responses, SCRs) in monkeys trained to perform target-selection (TS) tests. In each test, the animal was presented in successive trials with the same two unequally rewarded targets on a touch screen. The probabilistic contingencies of the rewards associated with each target rendered the selection of the best difficult. Our findings revealed SCRs time-locked to the arm movements toward the rewarded targets, occurring after the target touches. Parameters of the SCRs were stable when the uncertainty of the choices and of the outcomes varied. The results support the hypothesis that the physiological processes indexed by the SCRs are the correlate of anticipatory appetitive behavior. In contrast, there is no evidence that the SCRs reflect cognitive processes associated with the detection of the best target.

Animals↗

Principles of rat communication: quantitative parameters of ultrasonic calls in rats.

Ultrasonic calls used by rats during intraspecies communication have acoustic features, which can be selectively recognized by recipients, and possess a quantitative dimension reflecting the magnitude of the sender's response. This paper reviews basic principles of animal communication with particular attention to rat calls, and the features of ultrasonic calls, which could reflect such a quantitative aspect. Isolation calls of rat pups vary in frequency and duration and have changing sonographic structure over time. It is hypothesized that the quantitative "message" for the dam is encoded not only in the number of calls but also in frequency sweeps. The 22-kHz alarm calls of adults are characterized by a relatively constant sound frequency, marginal frequency modulation, and remarkable variability in call duration. It is hypothesized that quantitative aspect of these calls may be encoded in call length. Finally, the 50-kHz calls of adults, which are emitted in appetitive behavior are very short calls, with a relatively constant call duration, and a variable sound frequency. It is hypothesized that the peak frequency as well as the number of calls per time unit reflect the quantitative aspect in 50-kHz calls.

Aging↗

The development of dependence to an octapeptide somatostatin analog: contribution to the study of somatostatin analgesia.

This paper reports the phenomenon of dependence to a somatostatin octapeptide analog used for the treatment of acromegaly and severe headache. The mechanism of this dependence is still unknown, but could be based on the interaction of the somatostatin analog with opioid receptors. Analgesia may be at least partially supported by the opioid modulation of pain transmission, but also by general "appetitive" behavioral activation due to the effect of somatostatin on its receptors.

Acromegaly↗

Reduced cerebrospinal fluid levels of immunoreactive pro-opiomelanocortin related peptides (including beta-endorphin) in anorexia nervosa.

The discovery that the endogenous opioid peptides contribute to the modulation of appetitive behavior and neuroendocrine function has raised questions as to whether disturbances of opioids contributes to the pathophysiology of eating disorders. To assess central nervous system (CNS) beta-endorphin in patients with anorexia nervosa we measured cerebrospinal fluid (CSF) beta-endorphin concentrations before, and at intervals after weight correction. In addition, we measured three sister peptides (beta-lipotropin, adrenocorticotropic hormone (ACTH), and the N-terminal fragment) derived from the same precursor molecule, pro-opiomelanocortin (POMC) to determine whether possible disturbances might extend to sister peptides. Underweight anorectics (58 +/- 5% of average body weight (ABW), n = 10) had significantly lower CSF concentrations of all 4 peptides compared to healthy controls (102 +/- 10% ABW, n = 11). CSF concentrations of all 4 POMC-related peptides were found to be significantly increased when the same anorectics were restudied 4 to 6 weeks after weight gain (83 +/- 4% ABW). After weight gain, levels of CSF beta-endorphin, beta-lipotropin, and ACTH were similar to controls, whereas levels of CSF N-POMC remained significantly less than controls. Another group of women, previously underweight with anorexia nervosa, but weight-restored (93 +/- 11% ABW, n = 12) for greater than 1 year had CSF concentrations of all 4 POMC-related peptides that were similar to controls. We conclude that underweight anorectics have state-associated disturbances of CNS beta-endorphin as well as other POMC-related peptides. These abnormalities are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic alterations in behavior and neuroendocrine function.

Adrenocorticotropic Hormone↗

Augmentation of dietary fat preference by chronic, but not acute, hypercorticosteronemia.

Numerous studies have documented a role for corticosterone in appetitive behavior, including caloric intake and dietary fat preference. In the present study, we have examined the mechanism(s) underlying modulation of dietary fat preference by corticosterone. The results of these studies show a) an increased fat preference with increased basal urinary output, or decreased stimulation of corticosterone output on fasting, b) elevation of fat preference following chronic, but not acute, hypercorticosteronemia produced by exogenous corticosterone administration, and c) emergence of hypercorticosteronemia prior to the development of increased fat preference in developing rats. These observations have led us to suggest that increased fat preference after chronic hypercorticosteronemia may be secondary to changes in the levels or actions of agents known to affect fat intake.

Animals↗