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Urocortin: A Novel Player in Cardiac Control.

Urocortin is a potent regulator of cardiac function, with actions that are prolonged in experimental animals. These changes are mediated via binding to corticotropin-releasing factor receptors found in peripheral tissues. The effects of urocortin on behavior, appetite, inflammation, and the cardiovascular system suggest that this peptide may be an endogenous factor mediating actions previously attributed to corticotropin-releasing factor.

Journal Article↗

Sex differences in the effect of obesity on human plasma tryptophan/large neutral amino acid ratio.

BACKGROUND: The neurotransmitter serotonin (5-HT) contributes to the regulation of food intake and appetite behavior, and its rate of synthesis depends upon brain tryptophan (TRP) availability in relation to the large neutral amino acids (LNAAs). Thus, the ratio of TRP to the sum of LNAA (TRP/LNAA) will be representative of the 5-HT brain levels. Differences between men and women in the obesity-linked alterations in whole blood amino acid levels and compartmentation have been described. The aim of this work was to study the effect of obesity on brain TRP availability in men and women and to determine whether there are sex-linked differences. METHODS: The plasma levels of TRP and LNAAs in 42 men and 46 women (classified according to their body mass index (BMI) into lean, overweight and obese) have been determined by HPLC. RESULTS: The TRP/LNAA ratio shows a significant drop which is even more pronounced in men than in women as BMI increases. Moreover, the comparison of the values between the 3 BMI groups revealed that the drop in the TRP/LNAA ratio appears with overweight in men but only with obesity in women. CONCLUSION: These sex differences could affect hypothetical behavioral differences of feeling hunger when facing voluntary food restriction for weight loss in individuals of different genders and with varying degrees of obesity.

Amino Acids↗

The effects of background pattern and contrast on prey discrimination by the praying mantis Sphodromantis lineola (Burr.).

Tethered, adult female Sphodromantis lineola (Burr.) were presented with two groups of two-dimensional stimuli (i.e., 2-D lures) against various backgrounds. Lure Group 1 comprised various black rectangles in three different size arrays: each size array included a 2, 6, or 12 mm square, respectively, several 'worm' lures of a constant width (l2, edge perpendicular to the direction of movement, 3-30 mm), but varying in length (l1, parallel to the direction of movement, 6-114 mm), and several 'antiworm' lures of a constant length but varying width. Group 1 lures were presented against patterned backgrounds of similar luminance: one natural pattern mimicking foliage and the other a random geometric pattern of rectangles. Group 2 lures comprised various configurations and combinations of black and white lures which were presented against white, black, and natural pattern backgrounds. The appetitive behaviors of approaching and striking at a lure were dependent measures indicating that a stimulus was categorized as prey. For Group 1 lures, overall response rates to lures of the same size were enhanced by the natural pattern background rather than the geometric pattern background. Against the natural pattern background, worm lures were stronger releasers of predatory behavior than antiworm lures of the same size. Lure configuration (especially for the smallest array) was masked by the geometric pattern background, although worm versus antiworm discrimination was apparent with the largest size array. For Group 2 lures, lure-to-background contrast, as well as configuration, effected prey recognition. For instance, lures with low lure-to-background contrast ratios were weaker releasers than those with high ratios, and lures that were darker (versus lighter) than the background were stronger releasers. In addition, particular stimulus properties interacted to effect lure strength. For instance, a weak or strong releaser became stronger or weaker, respectively, when a more or less, respectively, preferred releaser was super-imposed. The results also suggest that S. lineola attends preferentially to the leading edge of a moving stimulus. These findings are in agreement with predatory behavior of praying mantises in the wild.

Animals↗

Altered expression of hypothalamic neuropeptide mRNAs in food-restricted and food-deprived rats.

Hypothalamic neuropeptides play a role in appetite and weight regulation. Food restriction for 2 weeks and food deprivation for 4 days were used as models to characterize the effects of weight loss on hypothalamic peptide gene expression in male and female rats. We used in situ hybridization to examine the mRNA levels of hypothalamic peptides which stimulate and inhibit food intake and found selective effects primarily in the arcuate nucleus. Neuropeptide Y (NPY) mRNA was increased and pro-opiomelanocortin (POMC) and galanin (GAL) mRNA were decreased in the hypothalamic arcuate nucleus and corticotropin-releasing hormone (CRH) mRNA was decreased in the hypothalamic paraventricular nucleus in male and female food-restricted and food-deprived rats. Food restriction produced larger changes in peptide mRNA expression than did food deprivation. Changes in NPY, POMC and CRH gene expression induced by food restriction were greater in male than female rats. Elevated NPY and reduced CRH gene expression may be a compensatory physiological response to restore food intake in food-restricted and food-deprived animals. The discrete changes in NPY, POMC, GAL and CRH gene expression in food-restricted and food-deprived animals suggest the involvement of these peptides in abnormal appetitive behavior and weight loss associated with human eating disorders.

Adrenocorticotropic Hormone↗

Absence of ghrelin protects against early-onset obesity.

The gut peptide ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, has been implicated not only in the regulation of pituitary growth hormone (GH) secretion but in a number of endocrine and nonendocrine functions, including appetitive behavior and carbohydrate substrate utilization. Nevertheless, recent genetic studies have failed to show any significant defects in GH levels, food intake, or body weight in adult ghrelin-deficient (Ghrl-/-) mice. Here we demonstrate that male Ghrl-/- mice are protected from the rapid weight gain induced by early exposure to a high-fat diet 3 weeks after weaning (6 weeks of age). This reduced weight gain was associated with decreased adiposity and increased energy expenditure and locomotor activity as the animals aged. Despite the absence of ghrelin, these Ghrl-/- mice showed a paradoxical preservation of the GH/IGF-1 axis, similar to that reported in lean compared with obese humans. These findings suggest an important role for endogenous ghrelin in the metabolic adaptation to nutrient availability.

Animal Feed↗

CSF cholecystokinin octapeptide in patients with bulimia nervosa and in normal comparison subjects.

Cholecystokinin octapeptide (CCK-8) appears to modulate appetitive behavior, and in rodents, anxiety-related behavior. The authors studied CCK-8 in patients with bulimia nervosa. CSF concentrations of CCK-8 were measured in 11 drug-free female patients with DSM-III-R-defined bulimia nervosa and in 16 normal subjects. The bulimic patients had significantly lower levels of CCK-8 than the comparison subjects. CCK-8 concentrations were inversely correlated with scores on the anger-hostility, anxiety, and interpersonal sensitivity subscales of the SCL-90-R. They were not significantly correlated with age, percentage of standardized average body weight, or mean weekly frequency of binge eating or vomiting. The results indicate that central CCK-8 abnormalities may play a role in the pathophysiology of bulimia nervosa.

Adult↗

Do domestic pigs in controlled environments contrafreeload?

Many experiments report that animals will work (lever press) for food in the presence of freely available identical food. This phenomenon has attracted the attention of applied ethologists because it seems to prove that animals have a need to express appetitive behavior. If this is the case, then it has implications for the provision of environmental enrichment for animals in captivity. In this experiment, we maintained 6 pigs in closed economy environments for three 120-hr choice periods in which they had continuous free access to operant and identical free food. In the experiment, we tested pigs using 2 different operant schedules, fixed ratio (FR) 5 and variable ratio (VR) 5. We used a VR schedule because many enrichment studies claim that unpredictability is an important characteristic that makes an enrichment device attractive. The results show that pigs exhibited a negligible level of contrafreeloading (M +/- standard error of the mean proportion = 0.05 +/- 0.01). Furthermore, there were no significant differences between FRs and VRs of reinforcement.

Animals↗

Mutation screening of the urocortin gene: identification of new single nucleotide polymorphisms and association studies with obesity in French Caucasians.

A linkage between obesity-related phenotypes and the 2p21-23 locus has been reported previously. The urocortin (UCN) gene resides at this interval, and its protein decreases appetite behavior, suggesting that UCN may be a candidate gene for susceptibility to obesity. We localized the UCN gene by radiation hybrid mapping, and the surrounding markers were genotyped in a collection of French families. Evidence for linkage was shown between the marker D2S165 and leptin levels (LOD score, 1.34; P = 0.006) and between D2S2247 and the z-score of body mass index (LOD score, 1.829; P = 0.0019). The gene was screened for SNPs in 96 obese patients. Four new variants were established. Two single nucleotide polymorphisms were located in the promoter (-535 A-->G, -286 G-->A), one in intron 1 (+31 C-->G), and one in the 3'-untranslated region (+34 C-->T). Association studies in cohorts of 722 unrelated obese and 381 control subjects and transmission disequilibrium tests, performed for the two frequent promoter polymorphisms, in 120 families (894 individuals) showed that no association was present between these variants and obesity, obesity-related phenotypes, and diabetes. Thus, our analyses of the genetic variations of the UCN gene suggest that, at least in French Caucasians, they do not represent a major cause of obesity.

Adult↗

Specificity of the neuroendocrine response to orgasm during sexual arousal in men.

We have demonstrated that sexual activity produces transient sympathoadrenal activation and a pronounced, long-lasting increase in prolactin in men and women. However, by analyzing endocrine alterations at 10-min intervals, a precise assignment of these changes to the pre-, peri- and postorgasmic periods was not possible. Thus, the current study aimed to accurately differentiate the endocrine response to sexual arousal and orgasm in men using an automatic blood collection technique with 2-min sampling intervals. Blood was drawn continuously before, during and after orgasm over a total period of 40 min in 10 healthy subjects and were compared with samples obtained under a control condition. Sexual activity induced transient increases of plasma epinephrine and norepinephrine levels during orgasm with a rapid decline thereafter. In contrast, prolactin levels increased immediately after orgasm and remained elevated throughout the experiment. Although oxytocin was acutely increased after orgasm, these changes were not consistent and did not reach statistical significance. Vasopressin, LH, FSH and testosterone plasma concentrations remained unaltered during sexual arousal and orgasm. These data confirm that prolactin is secreted after orgasm and, compared with oxytocin, seems to represent a more reliable and sustained marker for orgasm in man. The results further reinforce a role for prolactin either as a neuroendocrine reproductive reflex or as a feedback mechanism modulating dopaminergic systems in the central nervous system that are responsible for appetitive behavior.

Adolescent↗

Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

OBJECTIVE: To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. ANIMALS: 6 adult female alpacas. PROCEDURE: A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. RESULTS: Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

Administration, Oral↗

[Nutritional and metabolic status and dietetic evaluation in institutionalized elderly patients with non-insulin-dependent diabetes mellitus].

OBJECTIVE: To evaluate nutritional status and blood glucose level according to type of diet followed by elderly (> 65 years old) institutionalised patients with non insulin dependent diabetes mellitus (NIDDM). METHODS: A data collection questionnaire was administered to the staff of 80 Spanish geriatric facilities participating in this one-day cross-sectional study. Data collected included: age, gender, history of previous glucose control, type of antidiabetic treatment, body mass index (BMI), nutritional risk index (NRI), type of diet with patient's preference, nutritional status evaluation and biochemical parameters. RESULTS: Data from a total of 486 institutionalised elderly people (66.5% female) were collected with a mean +/- SD age of 80.8 +/- 7.5. Had a diabetic diet 93.3% of patients with no gender differences 55.7% were on oral antidiabetic treatment (53.9% females and 58.9% males, ns) and 24.7% on insulin therapy (24.5% females and 26.4% males, ns). Physical activity was presented in 86% of people with no gender differences. Exercise was practiced by people younger, 78.8 +/- 7.9 years, versus walking, 80.4 +/- 7.6 years or resting 82.1 +/- 7.3 years, p < 0.05. Both nutritional indexes, BMI and NRI, were equivalent in men and in women; 28.5 +/- 10.7 vs 28.1 +/- 7.6 and 103.5 +/- 12.9 vs 104.1 +/- 11.4, respectively. History glucose control was good in 68.8% of the sample with a trend towards significance between sexes (62.7% males, 71.7% females, p = 0.07) and significant differences according to type of diet; 70.7% diabetic versus 37.0% free diet, p = 0.0006). Eating behaviors (appetite and meal completeness) were similar in both males and females and in diabetic or free diet groups. Also, no differences were observed in patient preferences about diet according to type of diet (71% of diabetic patients always or almost always liked their food versus 82% of free diet patients) and either nutritional status (9.3% vs 15.6% in status I, 10.9% vs 12.5% in level II and 79.9% vs 71.9% in status III, respectively). The NRI, cholesterol, albumin and triglyceride levels were significantly higher in patients with high fat rate supplemented dietary intake than other supplemented diets. CONCLUSIONS: A high proportion of patients on a diabetic diet was observed in this study with no gender differences. Elderly NIDDM institutionalised patients on a diabetic diet showed a greater good history glucose control than patients on a free diet. Diabetic diet preference by these subjects is similar than free diet. A better nutritional risk control was shown in patients with high fat rate supplemented diet.

Aged↗

Opioid receptor modulation of a metabolically sensitive ion channel in rat amygdala neurons.

We have used single-channel patch-clamp recordings to study opiate receptor effects on freshly dissociated neurons from the rat amygdalohippocampal area (also called the posterior nucleus of the amygdala), an output nucleus of the amygdala implicated in appetitive behaviors. Dissociated cells included a distinct subpopulation that was 30-40 micrometer in diameter, multipolar or pyramidal in shape, and immunoreactive for neuron-specific enolase, mu opioid receptors, and galanin. In whole-cell perforated-patch recordings, these cells responded to low concentrations of mu opioid agonists with a hyperpolarization. In cell-attached single channel recordings, these cells expressed a large variety of K(+)-permeable ion channels, including 20-100 pS inward rectifiers and 150-200 pS apparent Ca(2+)-activated K(+) channels, none of which appeared sensitive to the presence of opioid drugs. In contrast, a 130 pS inwardly rectifying channel was selectively activated by mu opioid receptors in this same subpopulation of cells and was active only in the presence of opioid agonists, and inhibited in the presence of antagonists. Channels identical to the 130 pS channel in conductance and voltage sensitivity were activated in the absence of opioids, when the cells were treated with glucose-free medium or with the metabolic inhibitor rotenone. The sulfonylurea drug tolbutamide inhibited 130 pS channel openings elicited by opioids. Thus, a subpopulation of amygdala projection neurons expresses a metabolically sensitive ion channel that is selectively modulated by opiate receptors. This mechanism may allow opioid neurotransmitters to regulate ingestive behaviors, and thus, opiate drugs to influence reward pathways.

Amygdala↗

Ethanol, endocannabinoids, and the cannabinoidergic signaling system.

This article represents the proceedings of a symposium at the 2001 annual meeting of the Research Society on Alcoholism in Montreal, Canada. The chairpersons were Appa Hungund and George Koob. The presentations were (1) Role of endocannabinoids in ethanol tolerance, by Appa Hungund; (2) Modulation of cannabinoid receptor and its signal transduction in chronic alcoholism, by B. S. Basavarajappa; (3) Endocannabinoid involvement in the control of appetitive behavior, by George Kunos; (4) Regulation of voluntary ethanol intake by cannabinoid receptor agonists and antagonists in alcohol-preferring sP rats, by Giancarlo Colombo; (5) Role of endogenous cannabinoid system in alcoholism, by Fernado Rodriguez de Fonseca; and (6) Endocannabinoids and dopamine interactions in vivo, by Loren Parsons and George Koob.

Alcoholism↗

[Long-term toxicity experiment with tea for descending lipid and declining fat].

OBJECTIVE: To investigate the chronic toxicity of tea for descending lipid and declining fat (TDLDF). METHODS: 4 groups Sprague-Dawley rats had respectively been fed with distilled water and TDLDF in 7 g/kg (high dosage), 3.2 g/kg (middle dosage) and 1.5 g/kg(lower dosage) for 12 weeks, the latter were respectively equal to 100, 50 and 20 times clinical dosage. After ig 6, 12 weeks and 3 weeks after discontinuation, the behavior, appetite, excrement and urine, body weight, hematological and biochemical markers, coefficient of the main organs and pathohistological examination of the rats were investigated. RESULT: There were no significant differences of the above markers between each experimental group and the control group. CONCLUSION: The clinical recommended dosage of TDLDF is safe.

Animals↗

Relationships between the determinants of performance in serial feature-positive discriminations.

Three experiments using an appetitive behavioral observation procedure with rats investigated the effects of various pre- and postdiscrimination treatments on learning and performance in serial feature-positive discriminations. Previous work suggests that performance in this discrimination is based on feature-unconditioned stimulus (US) associations, feature-common element associations, and a conditional occasion-setting relation. Experiment 1 examined the effects of prediscrimination reinforcement of the various components of the discrimination. Experiments 2 and 3 investigated the effects of various postdiscrimination nonreinforcement and reinforcement procedures, respectively, on performance of previously established discriminative responding. The results of the present studies and those of previous work are interpreted to show that the conditional occasion-setting relation may be independent of feature-US associations and may not be dependent on feature-common element associations. The implications of assumming that rats used conditional information independently of simple associations are discussed.

Animals↗

Safety, efficacy, and duration of immunity induced in swine by use of an avirulent live Salmonella choleraesuis-containing vaccine.

An avirulent live Salmonella choleraesuis culture (SC-54) was evaluated for use as an effective vaccine in preventing salmonellosis caused by S. choleraesuis in pigs. Eighty-two pigs, 3 to 4 weeks old, were randomly assigned to 1 of 2 treatment groups, which were designated as either vaccinates or controls. After vaccination, all pigs were examined for fecal shedding of S choleraesuis, rectal temperature, and 10 clinical variables. Significant difference was not detected between vaccinated and nonvaccinated pigs for 14 days (phase I) after intranasal administration of the vaccine. Efficacy and duration of immunity were examined by intranasally challenge exposing respective pigs from either treatment group with a virulent field isolate of S choleraesuis at 2, 8, or 20 weeks after vaccination (phases II-IV). Pigs were again evaluated for 14 days after challenge exposure, and 10 clinical variables and rectal temperature were monitored. Surviving pigs were euthanatized and evaluated for gross lesions, and samples of 7 organs were collected. These organs samples were homogenized, and level of S choleraesuis infection was determined. After virulent challenge exposure during phases II-IV, the clinical status of the SC-54 vaccinates was significantly (P < 0.05) superior to that of nonvaccinates for rectal temperature, feces consistency, behavior, appetite, body condition, and mean score for the 10 clinical variables. Quantitative bacteriologic culture of the tonsil, lung, liver, spleen, mesenteric lymph nodes, ileum, and colon samples indicated consistent reduction of organ colonization in vaccinates; bacteria numbers in the mesenteric lymph nodes, lungs, and ileum were significantly (P < 0.05) reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Excretion of porcine reproductive and respiratory syndrome virus in semen after experimentally induced infection in boars.

Four boars intranasally inoculated with porcine reproductive and respiratory syndrome (PRRS) virus were monitored for 56 days after exposure for changes in semen characteristics and for the presence of virus in the semen. Clinically, 2 of 4 boars had mild respiratory signs of 1 day's duration after infection. Changes in appetite, behavior, or libido were not detected. All boars seroconverted on the indirect fluorescent antibody and serum virus neutralization tests by day 14 after inoculation. Virus was isolated from serum between days 7 and 14 after inoculation. During the monitoring period, semen volume decreased and pH correspondingly increased; however, this change began 7 to 10 days prior to infection. Differences in sperm morphologic features, concentration, or motility between the preinfection and postinfection samples were not observed. The PRRS virus was detected in semen at the first collection in each of the 4 boars (ie, 3 or 5 days after challenge exposure). Virus was detected in nearly all semen samples collected from the 4 infected boars through days 13, 25, 27, and 43, respectively. Neither gross nor microscopic lesions attributable to PRRS virus were observed in tissues collected at the termination of the experiment (day 56), and virus isolation results from reproductive tissues were negative.

Animals↗

Phasic firing of single neurons in the rat nucleus accumbens correlated with the timing of intravenous cocaine self-administration.

To examine potential neural mechanisms involved in cocaine self-administration, the activity of single neurons in the nucleus accumbens of rats was recorded during intravenous cocaine self-administration. Lever pressing was reinforced according to a fixed-ratio 1 schedule. On a time base comparable to the interinfusion interval, half the neurons exhibited phasic firing patterns time locked to the cocaine reinforced level press. For almost all neurons, this pattern consisted of a change in firing rate postpress, typically a decrease, followed by a reversal of that change. The postpress change was closely related to the lever press. Typically, it began within the first 0.2 min postpress and culminated within the first 1.0 min postpress. For a small portion of responsive neurons, the reversal of the postpress change was punctate and occurred within 1-3 min of either the last lever press or the next lever press so that firing was stable during much of the interinfusion interval. For the majority of neurons, the reversal was progressive; it began within 2 min after the previous level press, and it was not complete until the last 0.1-2.0 min before the next lever press. The duration of this progressive reversal, but not of the postpress change, was positively correlated with the interinfusion interval. Thus, in addition to exhibiting changes in firing related to the occurrence of self-infusion, the majority of neurons also exhibited progressive changes in firing related to the spacing of infusions. In a structure that has been shown to be necessary for cocaine self-administration, such a firing pattern is a likely neurophysiological component of the mechanism that transduces declining drug levels into increased drug-related appetitive behavior. It is, thus, a neural mechanism that may contribute to compulsive drug-maintained drug taking.

Animals↗