Chow Pellets Research Articles

A meprin inhibitor suppresses atherosclerotic plaque formation in ApoE −/− mice

Meprin is a member of the astacin family of zinc metalloendopeptidases. It is widely distributed in the body, and hydrolyzes and inactivates several endogenous vasoactive peptides, some of which could alter various functions of cells in the arterial wall. We assessed the influence of chronic meprin inhibition by daily administration of actinonin (5 mg/kg body weight per day; i.p.) on the development of atherosclerotic changes in ApoE −/− mice. Mice were fed a high-fat (21% fat), cholesterol-rich (1% cholesterol) Western-type diet for 16 weeks starting at 10 weeks of age. At 20 weeks of age, randomly selected ApoE −/− mice were treated with Western-type diet chow pellets supplemented with commercially available actinonin (meprin-I group) for 6 weeks; the diet of control ApoE −/− mice was supplemented with saline (placebo group). There was no difference in body weight, hemodynamic data and serum lipids between the two groups at the end of the dietary period. Meprin-I treatment was found to elevate levels of natriuretic peptides (NPs) in plasma and the vascular wall by radioimmunoassay. Meprin-I treatment also decreased plaque volume and suppressed lipid deposition in carotid arteries. Meprin-I treatment reduced production of reactive oxygen species (ROS) and apoptosis (which are associated with atherosclerosis) in the vascular wall. In in vitro experiments, meprin-I treatment increased NP function on cell apoptosis, proliferation, and intracellular ROS generation in the THP-1 cell line and primary vascular smooth muscle cells (VSMC). These results suggest that the meprin inhibitor actinonin may have a protective role in atherosclerosis, and that meprin inhibition may be therapeutically useful in atherosclerosis prevention. Suppression of degradation in the arteries of endogenously released NPs (particularly atrial natriuretic peptide and brain natriuretic peptide), or other kinins known to have anti-atherosclerotic actions, may at least partially contribute to the inhibitory effects of meprin-I on atherosclerotic changes.

Substance P-Mediated Expression of the Pro-Angiogenic Factor CCN1 Modulates the Course of Colitis

Substance P (SP) regulates important intestinal functions, such as mucosal permeability, motility, chloride secretion, and inflammation via the neurokinin-1 receptor (NK-1R). Previous reports showed that vascularization and expression of angiogenic factors are evident in the colonic mucosa of rats with colitis and patients with inflammatory bowel disease. Here we determined whether SP is associated with angiogenesis. Human NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) and mice with dextran sodium sulfate-induced colitis were used. We found that expression of the angiogenic factor CCN1 was increased in the colons of patients with Crohn's disease and ulcerative colitis. Mucosal extracts from inflammatory bowel disease patients induced human intestinal microvascular endothelial cell migration that was inhibited by blockade of CCN1 and its receptor integrin alphavbeta3. Both the degree of angiogenesis and CCN1 expression were elevated in the colons of mice with dextran sodium sulfate-induced colitis, which was reduced by treatment with the NK-1R antagonist CJ-12255. SP also increased CCN1 expression in NCM460-NK-1R colonocytes. SP exposure to human intestinal microvascular endothelial cells co-cultured with NCM460-NK-1R cells induced angiogenic activity that was inhibited by CCN1 silencing. In addition, intracolonic overexpression of CCN1 induced angiogenesis in mouse colon. Thus, SP mediates angiogenesis via CCN1 during colitis.

Combined effects of niacin and chromium treatment on vascular endothelial dysfunction in hyperlipidemic rats

Combined treatment with niacin and chromium has been found to have a protective effect against oxidative damage to different tissues of hyperlipidemic rats. But its effects on vascular endothelial dysfunction are less clear. This study was performed to investigate the effect of combined treatment with niacin and chromium on vascular endothelial dysfunction, with the aim of gaining insight to the mechanisms by detecting the expression levels of ox-LDL and LOX-1. Twenty-four male, 4-week-old Wistar rats were randomly divided into three groups: control group (CG; n = 8), high-fat group (HF; n = 8), and drug control group (DG; n = 8). In CG group, rats were fed with pellet chow. In HF group, rats were fed with high-fat diet for 12 weeks. In DG group, rats were fed with the same high-fat diet and treated with CrCl(3) x 6 H(2)O (250 microg/kg days) and niacin (100 mg/kg days) by gavage technique for 12 weeks. At the end of the 12th week, samples from aorta and blood were collected. In HF group, the serum levels of total cholesterol (TC), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL) and endothelin (ET) were higher, whereas the levels of high-density lipoprotein (HDL), serum NO were lower than those in CG group. The levels of serum TC, LDL, ox-LDL and ET decreased and HDL, NO levels increased in DG group when compared with HF group. The levels of LOX-1, ICAM-1 were also observed in abdominal artery. In HF group, the protein and mRNA expression of LOX-1, ICAM-1 were elevated comparing with CG group. In DG group, the protein and mRNA expression of LOX-1, ICAM-1 were decreased obviously, but still differed significantly from those in CG group. ox-LDL was related positively to TC, LDL, ET, ICAM-1 and LOX-1, but related negatively to NO and HDL. These findings indicated that combined treatment with niacin and chromium has potential therapeutic protection of endothelial function by down-regulating ox-LDL/LOX-1 signaling pathway.

Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder

Excessive consumption of highly palatable foods may contribute to the development of weight gain. Therefore medications that selectively suppress eating of such foods would be useful in clinical practice. We compared the effects of the glutamatergic antagonists memantine and MTEP to dexfenfluramine in baboons given periodic access to highly palatable food and ad libutum access to a standard chow diet. Three days a week baboons received a sugar-coated candy during the first meal and standard standard-diet chow pellets were available in subsequent meals. All baboons derived a greater amount of energy from the single single-candy meal than from the standard diet across an entire day. Pre-treatment with dexfenfluramine, memantine, and MTEP produced decreases in candy consumption without altering candy-seeking behaviour. At the same time, dexfenfluramine and memantine, but not MTEP, produced a decrease in seeking and consumption of standard chow pellets. Both memantine and MTEP are promising agents for the treatment of obesity.

A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine

Procedures for studying the effects of medications on satiation will assist the development of obesity medications. Develop a procedure for measuring satiation during consumption of bland and highly palatable food and determine the effect of acute intramuscular administration of dexfenfluramine (DFEN), which increases serotonin levels, and memantine (MEM), which blocks N-methyl-D: -aspartate receptors. A modified progressive ratio (PR) procedure was used to track changes in reinforcing strength when a food was consumed. The response requirement increased after each reinforcement, and reinforcing strength was estimated using the breakpoint (BP), which was the last completed response cost. There was one preferred food (sweet candy) and one chow pellet PR session per week. During each session, four male and four female adult baboons experienced three 1-h PR trials, separated by 30 min. Chow pellets were available at all other times. We examined the BP for one to 20 candies or chow pellets. Drug effects were examined when baboons had access to one and ten candies or chow pellets. BPs for candy were greater than for pellets. Varying the pellet/candy pieces per delivery produced an inverted U-shaped function on the first trial, i.e., maximal BP was observed for three items, and the BP for multiple items, but not a single item, decreased across trials, i.e., BP decreased with food intake and satiation. DFEN and MEM decreased responding with the greatest effects at ten deliveries, suggesting that DFEN and MEM enhanced satiation. Drugs that enhance satiation for several types of food may be particularly effective for decreasing food intake.

Chronic exposure to dietary sterol glucosides is neurotoxic to motor neurons and induces an ALS-PDC phenotype.

Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which beta-sitosterol beta-D: -glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC.

Differential inhibition of galanin- and ghrelin-induced food intake by i.c.v. GLP-1(7-36)-amide

Feeding regulation involves both anorectic and orexigenic neuropepetides mainly located in the hypothalamus. To gain further insight into the interaction between these two groups of regulators inhibition of feeding induced by glucagon-like peptide-1 (GLP-1) was examined during stimulation of food intake by equimolar doses of ghrelin and galanin. The experiments were carried out in freely feeding rats. Intracerebroventricular (i.c.v.) injections were accomplished through stereotaxically implanted cannulae aimed at the lateral cerebral ventricle. Food intake of standard rat chow pellets was subsequently recorded for 2 h. Ghrelin and galanin stimulated food intake significantly with no difference between these two peptides. During ghrelin stimulation GLP-1 inhibited feeding in doses between 0.015 and 1.5 nmol. During galanin stimulation of food intake a ten fold higher dose (0.15 nmol) was required to inhibit food intake. In conclusion equimolar doses of i.c.v. ghrelin and galanin are similarly effective stimuli of food intake when given alone. However in combination with an anorectic neuropeptide such as GLP-1 they have substantially different potencies of feeding stimulation. Such interaction could also be of interest for therapeutic strategies involving both regulating groups of neuropeptides.

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Escalation of drug consumption-a hallmark of addiction-has been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

Combined treatment with niacin and chromium caused a protective effect on the small-intestine tissue of hyperlipidemic rats

The present study investigated whether a combined treatment of niacin and chromium (III) chloride caused a protective effect on the intestine of hyperlipidemic rats. Rats were divided into four groups: (I) rats were fed with pellet chow, (II) with a lipogenic diet for 60 days, (III) with a lipogenic diet and treated with 100 mg/kg niacin and 250 μg/kg chromium chloride for 45 days by the gavage technique after experimental animals had became hyperlipidemic (15 days), and (IV) with pellet chow and treated with the same dose of niacin and chromium chloride for the last 45 days. Hyperlipidemic rats displayed a reduction of the intestinal glutathione level and an increase in intestinal lipid peroxidation levels, and in serum cholesterol, total lipid and phospholipids levels. However, treatment with niacin and chromium reversed the effect of hyperlipidemia. Light microscopy revealed compressed villi, oedema, mononuclear cell filtration, and vacuolization on the cytoplasm of epithelial cells in the jejunum of hyperlipidemic rats. Ultrastructurally, the disruption of arrays of rough endoplasmic reticulum cisternae, an increase and gathering in smooth endoplasmic reticulum, swelling in mitochondrial cristae and lipid vacuoles were detected in epithelial cells of hyperlipidemic rat jejunum. Despite individual differences, degenerative findings were decreased in hyperlipidemic rats given niacin and chromium. Niacin and chromium treatments had a protective effect on the intestine of the hyperlipidemic rats as well as a lipid-reducing effect.

Kinematic analysis of an appetitive food-handling behavior: the functional morphology of Syrian hamster cheek pouches

Prodigious food hoarding in Syrian hamsters Mesocricetus auratus Waterhouse is strongly linked to appetite and is made possible by large internal cheek pouches. We provide a functional analysis of the cheek pouch and its associated retractor muscle. Frame-by-frame analysis of videotaped pouch-filling behavior revealed multiple jaw cycles for each food item pouched and the use of more jaw cycles to pouch large food items ( approximately 2.5 g chow pellets) than small (corn kernels or sunflower seed with husks). These results stand in contrast to previously reported pouching kinematics in the externally pouched Dipodomys deserti, which uses only one jaw cycle per pouching event. Comparison of pouching and mastication in the same individuals also suggests that in Syrian hamsters, feeding jaw cycles are modulated to accommodate pouch filling primarily by the addition of a pause between fast open and fast close phases, which we call ;gape phase'. Contrary to previous assertions, the retractor muscle does not merely provide structural support for the full pouch during locomotion. Video analysis of ten hamsters with unilaterally denervated retractor muscles and electrophysiological study of an anaesthetized subject confirmed that retractor muscle activity during pouch filling increases pouching efficiency for food items subsequent to the first.

Chronic central leptin treatment increases protein intake in rats.

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fatless level while food intake increases to normal caloric levels, presumably in defense of lean body mass. This study evaluates food intake and macronutrient selection during this “fatless” phase of leptin treatment. Male Sprague-Dawley rats were maintained on standard pelleted rodent chow and injected daily with leptin (2.5 μg/3 μl, lateral ventricle) or vehicle solution (3 μl aCSF) until body weight reached a nadir and food intake returned to normal levels. Injections were then continued for 13 days, during which rats self-selected their daily diet from separate sources of carbohydrate (corn meal), protein (casein plus 0.6% methionine), and fat (corn oil). Despite similar caloric intakes on self-selection days 3–13, macronutrient choice differed profoundly in leptin and control rats. Leptin rats ate significantly more protein beginning on day 3, with intakes stabilizing between 45 and 55% of daily kcal. Controls preferred carbohydrate, eating almost no protein until day 10, then gradually increasing protein intake to about 20% of total kcals. Fat intake was stable at approximately 20% of total kcal in both groups. Sustained leptin-induced suppression of body fat stores may increase the utilization of protein for maintenance of energy homeostasis, promoting protein appetite. This protein appetite may contribute to the restoration (or derepression) of food intake that eventually occurs during chronic leptin treatment.

Protein appetite is increased after central leptin-induced fat depletion

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a "fatless" animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.

Decreased motivation to eat in µ‐opioid receptor‐deficient mice

Altered motivational processes might participate to the physiopathology of eating-related disorders. The endogenous opioid system is thought to mediate the hedonic properties of food intake. To assess the role for the micro-opioid receptor (MOR) pathway in the motivational properties of food intake, in the present study we tested wild-type and MOR-deficient mice (MOR-/-) in a nose-poke operant paradigm for chow or sucrose pellets. To avoid confounding factors linked to food restriction/deprivation experience, mice were always provided with food ad libitum. Although less MOR-/- than wild-type mice initiated operant behaviour, under a fixed ratio-1 (FR-1) reinforcement schedule the two genotypes showed similar patterns of food-driven nose-poking, indicating preserved cognitive abilities in MOR-deficient mice. However, during FR-3 and progressive ratio (PR) reinforcement experiments, MOR-/- mice showed lower levels of nose-poking for either chow or sucrose pellets than wild-type mice, indicating a crucial role for the MOR pathway in the motivational properties of food intake. Moreover, under the PR reinforcement schedule mice nose-poking for sucrose pellets showed higher genotype-independent breakpoint levels than mice working for chow pellets, indicating that the MOR pathway is not essential for hedonic processing of palatable food intake. Finally, MOR-/- mice did not differ from wild-type mice in the rate of operant responding extinction, further supporting the notion of unaltered cognitive abilities in the MOR-deficient mice. The present findings strongly indicate that the MOR pathway mediates the motivational properties of food intake, but it is not essential for hedonic processing of ingestive behaviour.

Leptin-Dependent Toll-Like Receptor Expression and Responsiveness in Preadipocytes and Adipocytes

Leptin, an adipokine mainly produced by adipocytes, has been well characterized with regard to its regulatory function on immune cells. Thus the question occurred of how adipocytes and preadipocytes interact with the immune system and whether or not this communication is regulated by leptin. With the present study we evaluated the Toll-like receptor (TLR) expression and TLR ligand-specific activation of murine preadipocytes and adipocytes in the presence [wild type (WT), 3T3L1] or absence of leptin (ob/ob) or leptin signaling (db/db). The ob/ob as well as db/db adipocytes and preadipocytes were characterized by a significant up-regulation of TLR1 to -9 expression when compared with WT cells. In WT preadipocytes the TLR responsiveness increased during maturation to adipocytes; however, stimulation of ob/ob and db/db cells resulted in a 10- to 20-fold higher interleukin-6 production. Signaling studies revealed, in addition to the increased TLR expression, alterations in the phosphoinositide 3 kinase signaling cascade in ob/ob and db/db cells as an explanation for this increased responsiveness. In conclusion, the present study indicates the expression and responsiveness of TLR1 to -9 in murine preadipocytes as well as adipocytes, both of which are strongly regulated by the adipokine leptin. In summary, these data further emphasize the role of fat tissue in the immune system.

Thyroid Transcription Factor-1 Facilitates Cerebrospinal Fluid Formation by Regulating Aquaporin-1 Synthesis in the Brain

In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5'-flanking region of the AQP-1 gene. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased AQP-1 synthesis and reduced CSF formation. In addition, blockade of TTF-1 synthesis increased survival of the animals following acute water intoxication-induced brain edema. These results suggest that TTF-1 is physiologically involved in the transcriptional control of AQP-1, which is required for CSF formation.

To sleep or eat: what is the body choice?

Epidemiological studies have shown a negative relationship between daily sleep hours and body mass index. However, rats differ from humans, since their weight does not increase with sleep deprivation. In the present study our aim was to investigate the body weight homeostatic control of rats, assessing their feeding behavior, hormones and glycogen storage responses to sleep deprivation. Recently we have shown that sleep deprived rats receiving chow pellets have impairment in food access and therefore a liquid diet have been offered in order to solve this inconvenience. We found a mild body weight reduction despite an increased food intake during 96h of sleep deprivation by platform technique. Furthermore, liver glycogen, blood leptin and insulin were reduced while glucagon and norepinephrine concentrations were increased in this condition. After 24h of sleep recovery the majority of these changes was restored despite of low food intake. These data suggest that sleep deprivation increases the energy demand and consequently decreases body weight. Body weight decrease triggers hormonal changes to activate catabolism and increase food intake. The failure in recovering weight under hyperphagic behavior led us to propose that factors such as sleep seek or stress overlap the feeding drive avoiding the equilibrium in energy balance during sleep deprivation. Research Support: FAPESP CNPq and AFIP.

The Effects of Combined Treatment with Niacin and Chromium on the Renal Tissues of Hyperlipidemic Rats

In this study, 12 months old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I were fed with pellet chow. Group II were fed with pellet chow and treated with 250 microg/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days. Group III were fed a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 2% sunflower oil added to the pellet chow, and given 3%alcoholic water for 60 days. Group IV were fed with the same lipogenic diet for 60 day sand treated by gavage technique to rats at a dose of 250 micro/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days, 15 days after experimental animals were rendered hyperlipidemic. At the 60th day, renal tissue and blood samples were taken from the animals. The sections were examined under light and electron microscopy. The degenerative changes were much more in the hyperlipidemic rats than the control group. The changes in renal tissue were also observed in hyperlipidemic animals given niacin and chromium. In the hyperlipidemic rats, renal glutathione levels decreased and renal lipid peroxidation levels, and serum urea and creatinine levels were increased. But, renal glutathione levels increased and lipid peroxidation levels and serum urea and creatinine levels decreased in hyperlipidemic rats given niacin and chromium. The purpose of this study was to investigate whether a protective effect of a combination of niacin and chromium is present on the renal tissue of hyperlipidemic rats or not. In conclusion, we can say that niacin and chromium do not have a protective effect on the morphology of the renal tissue of hyperlipidemic rats, except a protective effect on their biochemical parameters.

Lack of Food Anticipation in Per2 Mutant Mice

Predicting time of food availability is key for survival in most animals. Under restricted feeding conditions, this prediction is manifested in anticipatory bouts of locomotor activity and body temperature. This process seems to be driven by a food-entrainable oscillator independent of the main, light-entrainable clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus . Although the SCN clockwork involves self-sustaining transcriptional and translational feedback loops based on rhythmic expression of mRNA and proteins of clock genes , the molecular mechanisms responsible for food anticipation are not well understood. Period genes Per1 and Per2 are crucial for the SCN's resetting to light . Here, we investigated the role of these genes in circadian anticipatory behavior by studying rest-activity and body-temperature rhythms of Per1 and Per2 mutant mice under restricted feeding conditions. We also monitored expression of clock genes in the SCN and peripheral tissues. Whereas wild-type and Per1 mutant mice expressed regular food-anticipatory activity, Per2 mutant mice did not show food anticipation. In peripheral tissues, however, phase shifts of clock-gene expression in response to timed food restriction were comparable in all genotypes. In conclusion, a mutation in Per2 abolishes anticipation of mealtime, without interfering with peripheral synchronization by feeding cycles.

Effect of flavour of liquid Ensure diet supplement on energy intake in male SD rats

Outbred male Sprague–Dawley rats were provided with one of the four flavours of the liquid diet, Ensure, in addition to chow pellets, to examine whether differences in flavour lead to differences in energy intake i.e. degree of over-consumption. For half the rats, the Ensure supplement was provided for 14 days and then withdrawn for the final 8 days of the study, whereas the remaining animals were allowed to consume Ensure for 22 days. All four flavours of Ensure, chocolate, vanilla, coffee and asparagus, induced a sustained increase in daily energy intake of approximately 15%. There was an effect of flavour on initial consumption of the Ensure diet, with coffee and asparagus flavours being consumed less avidly than vanilla or chocolate. However, this effect was short-lived. Overall, there was no effect of flavour on body weight gain, energy intake from Ensure, total energy intake, body composition, or measured blood hormones and metabolites. Withdrawal of Ensure resulted in reductions in body weight gain, total energy intake, fat but not lean tissue mass, and concentrations of blood leptin, non-esterified fatty acids and triglycerides, but there was no effect of the flavour of Ensure previously supplied on any of these parameters. The ability of the liquid diet, Ensure, to stimulate long-term caloric over-consumption is not due to its flavouring. Rather, other attributes of Ensure must be more important, such as its intrinsic flavour, liquid formulation, macronutrient composition, and ease of ingestion, digestion and absorption.

Episodic-like Memory in the Rat

A fundamental question in comparative cognition is whether animals remember unique, personal past experiences. It has long been argued that memories for specific events (referred to as episodic memory) are unique to humans. Recently, considerable evidence has accumulated to show that food-storing birds possess critical behavioral elements of episodic memory, referred to as episodic-like memory in acknowledgment of the fact that behavioral criteria do not assess subjective experiences. Here we show that rats have a detailed representation of remembered events and meet behavioral criteria for episodic-like memory. We provided rats with access to locations baited with distinctive (e.g., grape and raspberry) or nondistinctive (regular chow) flavors. Locations with a distinctive flavor replenished after a long but not a short delay, and locations with the nondistinctive flavor never replenished. One distinctive flavor was devalued after encoding its location by prefeeding that flavor (satiation) or by pairing it with lithium chloride (acquired taste aversion), while the other distinctive flavor was not devalued. The rats selectively decreased revisits to the devalued distinctive flavor but not to the nondevalued distinctive flavor. The present studies demonstrate that rats selectively encode the content of episodic-like memories.