Drugs that enhance central serotoninergic transmission diminish elective carbohydrate consumption by rats.

We previously showed (Science 198:1178, 1977) that fenfluramine or fluoxetine, drugs thought to enhance serotoninergic transmission, selectively decrease the rat's consumption of carbohydrates, without affecting protein intake, when animals are given simultaneous access to diets differing in protein (5% vs 45%) and carbohydrate contents; in contrast, d-amphetamine lacks this selective effect. Present studies affirm this relationship using another serotoninergic drug, MK-212, and show that the suppression of carbohydrate intake occurs whether the test diets contain variable amounts of protein, or carbohydrates, or of both nutrients. Evidence is presented that rats given diet mixtures containing various proportions of carbohydrates have the ability to regulate their carbohydrate intakes (i.e., to choose to eat amounts of each diet that, taken together, will give them a desired proportion of carbohydrate), and that this ability is independent of whether or not the carbohydrate consumed has a sweet taste. It is proposed that serotoninergic neurons comprise part of a behavioral feedback loop, whereby the consumption of carbohydrate (which, by altering plasma amino acid patterns, accelerates serotonin synthesis in brain neurons) diminishes the rat's subsequent tendency to consume additional carbohydrates. Drugs that enhance central serotoninergic transmission can probably be substituted for dietry carbohydrate to activate this behavioral loop.     

Clonidine increases food and protein consumption in rats

Rats were given clonidine or its diluent, and allowed to eat freely from two isocaloric diets that differred in protein or carbohydrate content. Low clonidine doses (25–50 μg/kg) significantly increased total food and protein intake by rats given access to a high and a low protein diet. Several pairs of diets, differing in protein contents, were tested; clonidine's effect was greatest when a diet containing 30–45% protein was paired with one that was very low (5%) in protein. Higher clonidine doses (200 μg/kg) failed to modify either total food or protein intake. Clonidine had no effects on food or nutrient intake among animals given access to diets that differed in carbohydrate content (25 or 70% carbohydrate, plus 25% protein). In rats given access to only one diet, clonidine administration decreased food consumption when the diet was low in protein (5%), but increased consumption when the diet contained 25 or 50% protein. These data suggest that central noradrenergic synapses participate in the mechanisms controlling appetites for proteins. Clonidine may enhance protein intake by stimulating presynaptic alpha receptors, thus diminishing central noradrenergic tone. This effect on noradrenergic transmission is probably partly overcome by protein consumption, which increases brain tyrosine levels and thus can accelerate norepinephrine synthesis. Clonidine or related drugs may be useful clinically in treating diseases characterized by impaired appetite or increased need for protein.     

Effect of dietary protein and carbohydrate levels on growth,nutrient utilization and body composition in fingerling rohu,Labeo rohita (Hamilton)

Twelve experimental diets (D‐1 to D‐12) in a 4 × 3 factorial design having four protein levels (25, 35, 40 and 45%) and three carbohydrate levels (15, 25 and 35%) were formulated and fed to fingerling rohu, Labeo rohita (5.48 ± 0.02 g) for 60 days in three replicates at 2% BW per day. The best performance of fish in terms of weight gain (%), specific growth rate (SGR; % per day), feed conversion ratio (FCR) and protein efficiency ratio (PER) was recorded with diet D‐9 containing 40% protein and 35% dextrin as a source of dietary carbohydrate. In general, lower protein consumption per kilogram BW was observed at all protein levels with the rise of the dextrin level. The apparent digestibilities of protein and lipid were not affected by the dietary treatments. At the end of the experiment the body composition of animals from all treatments showed lower percentages of moisture and higher percentages of protein as compared to the initial values. A consistent rise in protein retention efficiency was noted in fish fed diets with increasing dextrin levels. The highest protein sparing effect was found in fish fed the diet containing 40% protein and 35% dextrin.     

Effects of dextrin and cellulose on feeding and reproduction in female brown-banded cockroaches, Supella longipalpa

Abstract Food consumption and reproduction were compared through two gonotrophic cycles in female brown-banded cockroaches, Supella longipalpa (F.), fed a standard rat food diet which had been serially diluted with methyl cellulose, alpha cellulose or dextrin. Females did not increase daily intake to compensate for dilution, and reproductive rate was highly dependent upon the degree of dilution of the diet. With increasing dextrin concentrations, digestibility increased, but reproductive rate, size and mass of oothecae, and efficiency of food utilization progressively decreased.
On diets containing 75% rat food and 25% methyl cellulose, females consumed minimal amounts of food and 80% of the females did not mate or produce oothecae within 30 days. On identical diets containing 25% alpha cellulose, food digestibility decreased and females ate significantly more than females fed 25% methyl cellulose, but less than females fed rat food. Many (65%) females fed 25% alpha cellulose produced oothecae which were smaller and took longer to form than in control females fed on rat food. At concentrations higher than 50% of either methyl or alpha cellulose daily intake was further reduced and females died rapidly.     

Inhibition of food intake in the rat

The effects of single oral administrations of tricyclic antidepressants (imipramine and desipramine), an atypical antidepressant (nomifensine), known anorexic agents, haloperidol, and diazepam on food intake were compared in Sprague-Dawley rats over a 4-day test period. The tricyclic antidepressants produced decreases in food intake during the total 4-day test period following their administration. In contrast, the anorexic agents (d-amphetamine, cocaine, mazindol, fenfluramine and quipazine), nomifensine, and haloperidol produced decreases in food intake only on the day of their administration. Diazepam produced an increase in food intake only on the day of its administration. In addition to revealing that high doses of antidepressants can decrease food intake, this model appears to show some specificity for tricyclic antidepressants.     

Effect of carbohydrate-enriched diet and subsequent food restriction on life prolongation in Fischer 344 male rats

Increased proportion of carbohydrates (dextrin) in the diet has a life prolonging effect upon male Fischer 344 rats; however, the effect of this diet appears only when the rats aged from 6 weeks to 6 months are on diet, after this treatment median survival of experimental animals increases by 96 days and the 10th percentile increases on the average by 10 days (n-60). Further maintenance of animals on the same diet has minimum effect: animals being on this diet throughout the whole life exhibit a median lifespan increase by 120 days and an increase in the 10th percentile by 41 days. However, if such animals aged 6 months are transferred to a restricted (60%) food intake regimen (control diet, not enriched with carbohydrate) a further increase in median and 10th percentile lifespan prolongation can be observed reaching 328 and 396 days, respectively as compared to controls. The effects of this early feeding (from 6 weeks to 6 months) with a carbohydrate-enriched diet available ad libitum and food restricted (60% controls) regimen fed from the age of 6 months onwards are additive, the final results being identical as if the animals are kept on the 60% food restricted intake throughout the whole life.     

Effects of dietary fibre on the intestinal absorption of dextrin, blood sugar level and growth of tilapia, Oreochromis niloticm × O. aureus

The roles of five different dietary fibres (cellulose, agar, guar gum, carrageenan and carboxy-methylcellulose) each as 10% wt/wt added into the diet, affecting the intestinal sugar absorption, blood sugar level and utilization of dextrin were studied in hybrid tilapia, Oreochromis niloticus × O. aureus ; dextrin and glucose were also included in the study as controls for comparison. There were seven dietary groups: each diet was fed to three aquaria each containing 15 fish. The experiment was carried out in a closed circulation, filtered, rearing system for 2 months. The results indicated that the weight gain percentage and food conversion ratio were significantly (P<0.05) lower in tilapia fed fibre-containing diets than those of tilapia fed dextrin or glucose diet. The intestinal absorption of carbohydrate and the blood sugar content of tilapia were low when diets contained fibre, regardless of the source.     

Biological Actions of Drugs Affecting Serotonin and Eating

The present status of knowledge on drugs affecting food intake and presumably acting via a serotoninergic mechanism is reviewed. The mechanism of action of these drugs is analyzed at the neurochemical level. All the drugs, to various extents, inhibit the uptake of serotonin (5HT), increase the release of 5HT and decrease brain levels of 5HT and 5HIAA. However, the underlying mechanisms are not identical as exemplified by comparisons made with d-fenfluramine, d-norfenfluramine, fluoxetine, sertraline and paroxetine. An analysis of the role of 5HT in the inhibition of food intake reveals that only d-fenfluramine is inhibited by antiserotonin agents. The role of the different 5HT receptor-subtypes in this antagonism is discussed. More selective 5HT antagonists are needed to establish which 5HT receptor(s) controls food intake.     

Different diets and amino acid supplementation do not affect the voluntary consumption of ethanol by rats

The effects of four different diets (control diet: 19.5% protein, 60.5% carbohydrate, 10% fat; diet I: 65% protein, 10% carbohydrate, 10% fat; diet II: 5% protein, 76% carbohydrate, 10% fat; diet III: 20% protein, 69% carbohydrate, 1% fat; diet IV: 69% protein, 15% carbohydrate, 1% fat) and supplementation with 3 amino acids (tryptophan: 150 mg/kg/d; arginine: 400 mg/kg/d; taurine: 380 mg/kg/d) on the voluntary consumption of ethanol were investigated in rats using the 2 bottle method. First, rats received the control diet and diets I, II, III and IV for 20 days with a choice of ethanol for the last 6 days only. Ethanol consumption was similar in all dietary groups. Second, rats received the control diet for 8 days followed by diets I, II and IV for another 8 days. Ethanol was offered throughout both periods. The switch to the special diets did not affect ethanol consumption. Third, rats received a control diet with arginine, tryptophan or taurine added to the drinking fluids for 16 days with a choice of ethanol for the last 5 days; thereafter supplementation stopped but the ethanol choice remained. No difference in the voluntary intake of ethanol was noted but ethanol consumption fell after cessation of arginine supplementation. In conclusion, diets differing greatly in their composition or supplementation with these 3 amino acids did not affect the voluntary choice of ethanol by rats in a significant manner.     

Early feeding of carnivorous rainbow trout (Oncorhynchus mykiss) with a hyperglucidic diet during a short period: effect on dietary glucose utilization in juveniles

Based on the concept of nutritional programming in higher vertebrates, we tested whether an acute hyperglucidic stimulus during early life could induce a long-lasting effect on carbohydrate utilization in carnivorous rainbow trout. The trout were fed a hyperglucidic diet (60% dextrin) at two early stages of development: either at first feeding (3 days, stimulus 1) or after yolk absorption (5 days, stimulus 2). Before and after the hyperglucidic stimulus, they received a commercial diet until juvenile stage (>10 g). Fish that did not experience the hyperglucidic stimuli served as controls. The short- and long-term effects of the stimuli were evaluated by measuring the expression of five key genes involved in carbohydrate utilization: alpha-amylase, maltase (digestion), sodium-dependent glucose cotransporter (SGLT1; intestinal glucose transport), and glucokinase and glucose-6-phosphatase, involved in the utilization and production of glucose, respectively. The hyperglucidic diet rapidly increased expressions of maltase, alpha-amylase, and glucokinase in stimulus 1 fish and only of maltase in stimulus 2 fish, probably because of a lower plasticity at this later stage of development. In the final challenge test with juveniles fed a 25% dextrin diet, both digestive enzymes were upregulated in fish that had experienced the hyperglucidic stimulus at first feeding, confirming the possibility of modification of some long-term physiological functions in rainbow trout. In contrast, no persistent molecular adaptations were found for the genes involved in glucose transport or metabolism. In addition, growth and postprandial glycemia were unaffected by the stimuli. In summary, our data show that a short hyperglucidic stimulus during early trout life may permanently influence carbohydrate digestion.     

The influence of estradiol and diet on small intestinal glucose transport in ovariectomized rats

Although gender differences exist for intestinal absorption of nutrients and drugs, the possible role estradiol may play in modulating nutrient transport has not been established. Therefore, small intestine glucose transport was measured 1 week after administering estradiol to ovariectomized rats fed diets high in carbohydrate (C) or protein (P). Rats treated with estradiol ate 21% less (P<0.05) and lost body mass (7%; P<0.05) but did not have smaller intestines. Administration of estradiol increased rates of glucose transport, but only when the rats were fed the C diet. These findings indicate that estradiol causes a disconnect between food intake and the dimensions and nutrient transport capacities of the small intestine. Furthermore, the responses to estradiol are influenced by diet composition, are not of the same magnitude for rats and dogs, and can be predicted to affect systemic availability of nutrients and drugs.     

Effect of long-term restriction of protein intake,from gestation onward,on free-choice consumption of ethanol by rats

Long-term (including gestational and lactational) restriction of protein (8% of diet) significantly lowered the absolute and relative consumption of 6% ethanol (EtOH) in a two-bottle, free-choice (H₂O vs EtOH) situation during a 76-day test period. This difference in response between rats fed the low protein diet and those fed an isocaloric normal protein (24%) diet became non-significant in two subsequent 100-day test periods. Statistical analysis of observations on individual performance indicated that regularity, cyclicity, and duration of drinking in each animal was random over all three time intervals for both groups. The early, significantly lower EtOH consumption by the protein-restricted group may be due to a paucity of EtOH-metabolizing enzymes in brain and liver, thereby prolonging the CNS effects of lower doses of EtOH consumed. The disappearance of this difference in subsequent test periods may reflect either a behavioral or metabolic adaptation in the developing protein-deficient rat.     

Effect of clofibrate feeding on some lipogenic enzyme activities induced by high carbohydrate diet

Clofibrate administration by stomach tube or intraperitoneally for 3 successive days to rats fed standard diet or starved for 72 hr caused about 2-fold increase of malic enzyme activity in the liver and adipose tissue. The drug administered by stomach tube (but not intraperitoneally) to the rats fed fat free-high carbohydrate diet significantly blocked the inducing effect of the diet on malic enzyme activity in both tissues. Clofibrate blocked the induction by fat free-high carbohydrate diet of hexose monophosphate shunt dehydrogenases and ATP-citrate lyase in the liver. The amount of fat free-high carbohydrate diet consumed by rats received clofibrate by stomach tube was much less than by untreated animals. It is concluded therefore that the significant decrease of food consumption by rats receiving clofibrate by stomach tube is responsible for the inhibitory effect of the drug on some lipogenic enzymes activity induced by fat free-high carbohydrate diet.     

High-moisture diet for laboratory rats: nutrient analysis, growth, and organ weights.

A diet (KSC-25) to be sterilized by irradiation was formulated to contain 66% moisture and to provide the required nutrients for growing rats. Analyses of the irradiated dry diet provided data to evaluate its nutrient content. The diet was evaluated for its ability to supply all nutrients, including water, required by immature rats. Sixteen Sprague-Dawley rats were fed the high-moisture diet with or without access to a water bottle. Rats (n = 16) fed an irradiated purified diet in a meal form with access to a water bottle were the control animals. Feed efficiency, food and water consumption, and growth rate data were collected during the 28-day study. Organ weights were collected on day 28. The test diet met or exceeded the National Research Council (NRC) estimated nutritional requirements for immature laboratory rats. The 66% moisture KSC-25 diet provided all nutrients, including water, required by weanling male Sprague-Dawley rats for growth equivalent to the established purified diet.     

Intestinal adaptation to diet in the young domestic and wild turkey (Meleagris gallopavo)

The short-term effects of diet on jejunal growth, alanine transport rate, and leucine aminopeptidase activity (LAP) were compared in the domestic and wild turkey poult. One-day-old poults of each strain were fed diets of high vs., low protein, with carbohydrate varied to maintain isocaloric conditions. Prior to feeding, relative jejunal mass and alanine transport rates were not significantly different in the two turkey strains, whereas LAP activity was 270% higher in wild poults. After feeding for 72 h, relative jejunal mass doubled in both turkey strains. In domestic turkeys, alanine transport rate and LAP activity were reduced by approximately 42% and 25%, respectively, in poults fed a 24% protein-69% carbohydrate diet vs. a 49% protein-35% carbohydrate diet. Analysis of the combined data from feeding experiments revealed that alanine transport rate was not correlated with total food, protein or lipid intake, but was negatively correlated with carbohydrate consumption (P<0.05). In wild turkeys, neither alanine transport rate nor LAP activity were altered by diet. These results reveal that domestic turkey hatchlings can modulate protein digestive and absorptive functions as protein/carbohydrate composition of the diet changes and suggest that high dietary carbohydrate down-regulates the intestinal alanine transporter.     

Effects of Phytic Acid and Exercise on Some Serum Analytes in Rats Orally Exposed to Diets Supplemented with Cadmium

Cadmium is an environmental pollutant of increasing worldwide concern. It has been reported to be high in the soil where food crops are grown in some parishes of Jamaica. Surprisingly, no adverse effect of cadmium has been reported among the Jamaican population. However, phytic acid has also been shown to be high in some food crops grown in Jamaica. In this study, we evaluated the effects of phytic acid (1 %) and exercise on the metabolism of cadmium (5 mg cadmium/kg body weight) in rats. Five groups of rats were fed as follows: rats fed control diet, control diet supplemented with cadmium and subjected to exercise, control diet supplemented with phytic acid plus cadmium and subjected to exercise, control diet supplemented with cadmium plus phytic acid, and control diet supplemented with cadmium only. The animals were fed for 4 weeks and then sacrificed. Blood samples were collected for some biochemical assays. Percentage weight loss (28.42 %) was greatest in the group that had cadmium supplement only. The group fed control diet supplemented with cadmium only displayed increased liver enzymes and electrolytes except for the significant decrease in bicarbonate compared to other test groups. Similarly, blood urea nitrogen and uric acid were increased in the group fed cadmium supplement only compared to other test groups. Total cholesterol trended downwards in the test groups compared to control. These observations suggest that consumption of diet high in phytic acid with relatively high physical activity may be protective against the adverse effects of cadmium.     

Patterns of food intake and self-selection of macronutrients in rats during short-term deprivation of dietary zinc

Although it has been known for more than 50 years that zinc (Zn) deficiency regularly and consistently causes anorexia in many animal species, the basic mechanism(s) that cause this phenomenon still remain(s) an enigma. The following studies describe feeding behavior in the early stages of zinc deficiency in the rat model. In one experiment, we used computerized feeding monitors that measured the intake of individual rats at 10-min intervals over 24-hr periods. Male rats were acclimated to the cages and fed a Zn-adequate egg-white-based diet, or a similar diet with <1.0 mg Zn/kg. Food intake was monitored for seven, consecutive 24-hr periods. The 24-hr food intake pattern of the Zn-deprived rats did not differ from the controls; they simply ate less food, mainly during the night hours, with no differences between groups during the day. Although Zn-deprived rats ate less food than controls, the percentage of total diet consumed during night and day did not differ between groups. In another experiment, we simultaneously offered male rats three isocaloric diets with different macronutrient compositions and with or without adequate Zn, and measured the amount of each diet selected during seven, 24-hr periods. The three diets contained either 57% protein from egg white, 30% fat from soybean oil, or 80% carbohydrate from a combination of starch, hydrolyzed starch, and sucrose. For the first four days on experiment, rats selected similar amounts of each diet. Then the Zn-deprived rats began to select only 50% as much of the protein diet as the controls. Similar results were obtained when the data were expressed on the basis of each macronutrient as a percentage of the total diet selected. Zn-deprived rats selected a diet that contained 8% protein, 73% carbohydrate, and 6% fat while the Zn-adequate rats selected 12% protein, 69% carbohydrate, and 6% fat. Fat intake was not affected by Zn-deprivation. The results confirm our previous findings, and are discussed in terms of Zn-deprivation blunting the pathways of signal transduction that involve the peptide hormones known to affect food intake regulation.     

Pharmacological blockade of serotonin 5-HT₇ receptor reverses working memory deficits in rats by normalizing cortical glutamate neurotransmission

The role of 5-HT₇ receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT₇ antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT₇ receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission.     

饲料中糖水平对不同食性海水鱼类PEPCK基因表达和酶活性的影响

磷酸烯醇式丙酮酸羧激酶(Phosphoenolpyruvate carboxykinase, PEPCK, E.C.4.1.1.32)是水生生物糖异生代谢的关键限速酶. 实验以杂食性罗非鱼(Oreochromis niloticus)、温和肉食性卵形鲳鲹(Trachinotus ovatus)、凶猛肉食性军曹鱼(Rachycentron canadum)三种不同食性海水养殖鱼类为研究对象, 以糊精为饲料糖源, 分别设置不同饲料糖添加水平(低糖组LD、中糖组MD、高糖组HD)等氮等能饲料, 每种鱼分别随机选取60尾体格均匀的幼鱼进行为期8周的饲养实验, 同时克隆卵形鲳鲹胞质型PEPCK基因cDNA全长序列, 以期探讨不同饲料糖水平对不同食性鱼类PEPCK活性及其mRNA表达的影响. 结果显示: 卵形鲳鲹PEPCK基因cDNA共2652 bp, 含1个编码624个氨基酸的开放阅读框, 三种不同食性海水鱼类PEPCK的生物信息学比较分析显示相似度达90%以上, 在结构和功能上具有较高的保守和同源性. 养殖实验结果显示: 随着饲料糖水平的增加, 三种鱼肝脏中PEPCK酶活性均降低, 其中卵形鲳鲹、军曹鱼HD组PEPCK活性比LD组分别显著降低28.05%和26.03% (P0.05). 而其肝脏中PEPCK mRNA表达水平同样均随饲料碳水化合物水平增加而受到抑制, 其中罗非鱼、卵形鲳鲹、军曹鱼中LD组PEPCK的mRNA分别是HD组的100倍、4.3倍和4.77倍. 结果表明鱼类的糖异生能力可能与其食性有关, 三种鱼PEPCK酶活性与基因表达量随着饲料糖水平的增加而受到显著抑制, 且mRNA表达抑制程度随食性不同而具有较大差异, 以杂食性罗非鱼受抑制程度最高, 凶猛肉食性军曹鱼受抑制程度最低.