Differential effects of amphetamine and fenfluramine on dietary self-selection in rats

Daily caloric intakes and dietary self-selection of the three macronutrients, protein, fat and carbohydrate were examined in female rats following administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg, IP) or fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg, IP). Animals were maintained on ground Purina Chow or one of two self-selection regimes, one with a high-caloric fat ration (7.85 kcal/g) and the other with a fat ration isocaloric to the carbohydrate and protein rations (3.76 kcal/g). Animals received drug injections at the beginning of a daily 8-hour feeding period with nutrient intakes measured at 2, 4 and 8 hrs following injections. While both amphetamine and fenfluramine led to dose-related decreases in total caloric intakes, the two drugs resulted in different temporal patterns of feeding. Amphetamine produced its greatest effect on caloric intake during the first 2 hours of the feeding period, whereas fenfluramine suppressed caloric intake equivalently across the 8-hour feeding period. The two anorectic drugs also led to different patterns of nutrient choice. When animals were given the high-caloric fat ration, amphetamine selectively decreased fat intake while fenfluramine produced decreases in both protein and fat intakes, sparing carbohydrate intake. In contrast, when animals were given the isocaloric fat ration, amphetamine resulted in a general suppression of nutrient intakes while fenfluramine led to a sustained decrease in fat intake with a relative sparing of protein and carbohydrate consumption.     

Response of guinea pig respiratory tract to inhalation of submicron zinc oxide particles generated in the presence of sulfur dioxide and water vapor

Guinea pigs were exposed for 3 hr to submicron zinc oxide aerosols generated in the presence of water vapor and 1 ppm sulfur dioxide. After exposure to the aerosol containing 5 mg/m³ of zinc oxide, the animals developed transient pulmonary edema accompanied by increased permeability of the respiratory epithelium to macromolecules and increased DNA synthesis in the terminal bronchioles, indicated by an elevated labeling index on autoradiographs. Peribronchiolar edema with cellular infiltrates was present after exposure to the aerosol containing 25 mg/m³ of zinc oxide and significant increases in the labeling index were noted for epithelial cells of the bronchi, bronchioles, and alveoli. The changes coincided with functional abnormalities detected in complementary physiological studies.     

The effects of dietary gum tragacanth in man

Following a 7-day control period, 5 male volunteers consumed 9.9 g gum tragacanth (GT) daily for 21 days. The GT was well tolerated and there were no adverse effects in any of the volunteers. The daily intake was very high in relation to the minor amounts of GT (estimated at 2 g per person per annum) likely to be ingested as a foodstuffs additive. The wide range of measurements made before and at the end of the test period show that the ingestion of GT had no significant effect on any of the following: plasma biochemistry; haematological indices; urinalysis parameters; glucose tolerance; serum cholesterol, triglycerides and phospholipids; breath hydrogen and methane concentrations. The intestinal transit time decreased and faecal fat concentration increased (P less than 0.01) for 4 subjects. The faecal wet and dry weights increased in all subjects (P less than 0.01). These changes may be of nutritional and physiological interest but do not reflect any adverse toxicological effects arising from the ingestion of large daily doses of GT.     

Toxicological evaluation of compounds found in food using rat renal explants

A rat kidney expiant system was developed and its respiratory characteristics in the presence and absence of a series of compounds found in food were studied. Cubes taken from the whole kidneys of male Osborne-Mendel rats were incubated under sterile conditions for up to 18 hr. The respiratory activity of these expiants after incubation was measured by determining the amount of ¹⁴CO₇ evolved as a result of the metabolism of [¹⁴C]glucose. Changes in membrane permeability as a result of treatment were assessed by measuring the total protein content in the medium. Measurements of respiratory activity showed that the biochemical integrity of the control expiants was well maintained over the test period. Various compounds were tested at a range of concentrations from 0·1 to 1·0 mM. In the initial screen, several of the compounds tested at 1mM—butylated hydroxytoluene (BHT), butylated hydroxy-anisole (BHA), DDT, polychlorinated biphenyl (Aroclor 1254), patulin, zearalenone and cadmium chloride—markedly inhibited respiration; neither ascorbic acid nor caffeine was effective at this concentration. Two of the fat-soluble compounds, DDT and zearalenone, inhibited respiration at concentrations of 0·1 and 0·25 mM concentrations, respectively, while patulin, a water-soluble mycotoxin, did not give significant inhibition at concentrations below 0·5 mM. In some cases, e.g. patulin and BHA, the dose-response curves appeared to be bimodal, with stimulation of respiration occurring at lower concentrations. The two mycotoxins, patulin and zearalenone, and the antioxidant BHA produced losses of cellular protein at concentrations of 1·0, 0·50 and 1·0 mM, respectively, indicating membrane perturbation. Thus, this kidney expiant system responded consistently to a variety of known toxins and can be considered as another in vitro method of determining which compounds show the potential for in vivo toxicity.     

Hypophagic and Dipsogenic Effects of Central 5-HT Injections in Pigeons

The present work describes a series of experiments designed to examine the possible role of central 5-HT circuits in the control of feeding and drinking in pigeons. Acute effects (within 1 h) of intracerebroventricular (ICV) injections of 5-HT (0, 9.7, 19.4, 38.7, 77.5, 155, and 310 nmol) in 24-h food-deprived (24FD) pigeons included strong hypophagic and dipsogenic responses at the three higher doses. Total food intake and the duration of feeding behavior were reduced, and latency for the start of eating increased. Total 1-h water intake in 5-HT–treated pigeons usually increases to reach a volume equivalent to 10% of their body weight. Similarly, potent dipsogenic effects of ICV 5-HT, but no food intake decreases, were observed in food-satiated animals. Feeding behavior induced by ICV injection of adrenaline (30 nmol) in satiated pigeons was abolished by previous (20 min before) ICV 5-HT (155 nmol) injections. Catecholamine treatment did not affected the dipsogenic effect of 5-HT injections. Decreases in food intake were similarly observed after ICV or subcutaneous injections of equimolar 5-HT doses (155 nmol) in 24FD pigeons, but systemic 5-HT injections evoked no drinking behavior. Central injections of the 5-HT_2a/2c agonist DOI (56 nmol) induced similar decreases in duration and amount of food intake in 24FD animals. No dipsogenic effect was observed with either DOI doses. In 24FD pigeons, the 5-HT_1a agonist 8-OH-DPAT (30.5 nmol) induced strong dipsogenic effects, as well as increase in food intake duration. These data may indicate an involvement of 5-HT circuits in food intake as well as in water intake control systems in the pigeon, and that serotoninergic effects in these functional domains are mediated by independent mechanisms.     

The effects of food deprivation and incentive motivation on blood glucose levels and cognitive function

The current study investigated the relationships between blood glucose levels, mild food deprivation, sympathetic arousal, and cognitive processing efficiency. Subjects (n = 82) were randomly assigned to four experimental conditions, comprising combined manipulations of food deprivation and incentive motivation. Baseline and mid-session measurements of blood glucose, blood pressure and pulse rate were taken. Subjects completed a number of measures of cognitive processing efficiency and self report measures of affective and somatic state. Although glucose levels were lowered following food deprivation, there was no significant detrimental effect of food deprivation on task performance. However, improved recognition memory processing times were associated with deprivation. Incentive motivation was associated with faster simple reaction times and higher diastolic blood pressure. There were no significant relationships between glucose levels and task performance, further supporting the hypothesis that the brain is relatively invulnerable to short food deprivation. Received: 12 February 1997 / Final version: 7 May 1997     

Nalmefene decreases meal size, food and water intake and weight gain in Zucker rats

Opioids are proposed to play a role in the control of food intake since administration of opioids increase food intake while administration of opioid antagonists decrease food intake. In these experiments responses to a new opioid antagonist, nalmefene, were measured in Zucker obese and lean rats. In obese male rats 1 mg/kg nalmefene decreased the size of the first meal after a 10-hr fast and decreased 14-hr food intake, indicating nalmefene is relatively long-acting. Administration of 1 mg/kg nalmefene daily for 7 days decreased average meal size and daily food intake and increased meal frequency; feeding responses on day 7 were similar to those on day 1, suggesting a lack of development of tolerance. Food and water intake and weight gain during a 3-week treatment period were decreased more in lean rats by low doses of nalmefene (up to 0.25 mg/kg) and more in obese rats by higher doses of nalmefene (0.50 mg/kg). These responses to a new opioid antagonist further support a possible role for opioids in the control of food intake.     

Amount of feeding activity and size of meals in free-feeding rats

Instrumentation is described for simultaneous measurement of feeding duration (time actually spent feeding during a nominal meal) and weight of food eaten in individual meals throughout 24-hr periods in free-feeding rats. These variables were measured in two rat strains. Meal weight cannot usefully be estimated directly from meal duration (total time from beginning to end of a nominal meal) or from meal feeding duration. An adjustment procedure is described that removes systematic error and allows a useful estimate to be made from meal feeding duration. The discrepancy remaining between measured and estimated meal size is quite large and is a measure of the independence of control of food intake and control of the behavioral output of feeding.     

Amphetamine Anorexia and Hypothalamic catecholamines in genetically obese mice (obob)

Genetically obese mice (obob) and their lean littermates were acclimated to a restricted food-access schedule of six hours and then treated with various doses of amphetamine (0, 3, 5 or 10 mg/kg). Saline-treated obob mice maintained on this schedule retained the primary characteristics of obob mice fed ad lib, i.e., hyperphagia, hyperglycemia, elevated hypothalamic norepinephrine (NE) levels. Both lean and obese mice treated with amphetamine showed a dose-dependent decrease in food intake and hypothalamic NE levels. In obob mice amphetamine treatment reduced food intake and hypothalamic NE levels to values which were not significantly different from those of similarly treated lean mice. When the drug dose was administered on a body weight basis, however, brain amphetamine levels were twice as high in obob as in lean mice. When the amphetamine dose was adjusted to produce approximately equivalent brain levels of amphetamine in obob and lean mice, the obob mice ate significantly more than lean mice. The results indicate that amphetamine is an effective anorectic agent capable of reducing food intake, body weight, and hypothalamic NE levels in obob mice.     

Gonadal hormones and behavioral regulation of body weight

Gonadal hormones have important effects on the behaviors that determine body weight in laboratory rats (i.e., eating, locomotor activity, and thermoregulatory behavior). These effects are most evident in the female where there are consistent, predictable changes in these behaviors which are correlated with fluctuations in plasma hormone levels during estrous cycles, puberty, pregnancy, or after gonadectomy and replacement therapy. Estradiol, which seems to be the principal ovarian steroid affecting body weight, may act directly on separate neural loci to: (a) inhibit food intake and (b) stimulate locomotor activity, possibly by lowering the set-point of a hypothalamic lipostat. Estradiol does not affect eating and running in prepubertal female rats, perhaps because of influences of pituitary hormone(s) at this age. Ovarian hormones also alter the taste preferences of rats and may be responsible for the changes in self-selection of dietary components during different reproductive states. Some implications of this research are discussed and possible directions for future research suggested.