Feeding and macronutrient selection patterns in rats: adrenalectomy and chronic corticosterone replacement

To analyze further the role of corticosterone (CORT) in the control of feeding behavior, we examined the impact of adrenalectomy (ADX) and chronic CORT implants on the food intake and macronutrient self-selection patterns of adult male rats at different periods of the diurnal cycle. Consistent with a separate study of acute CORT injection in ADX rats (Kumar and Leibowitz, 1988), the present findings indicate that ADX significantly attenuated the rats' daily (24 hr) ingestion of all three macronutrients, namely, protein, carbohydrate and fat. However, food intake in the dark cycle, specifically during the first few hours after dark onset, was significantly more affected (-70%) than feeding in the later dark and light periods (-25%). Moreover, during this early dark time when circulating CORT level normally peaks, ADX appeared to have its strongest suppressive effect on carbohydrate ingestion. Chronic subcutaneous CORT implants in the ADX animals reversed these effects of surgery and generally restored the rats' eating patterns to that of the cholesterol-implanted SHAM animals. These findings suggest that CORT exerts a decisive influence on caloric intake, on the diurnal pattern of feeding, and on appetite for specific macronutrients. The impact of CORT on carbohydrate intake is apparent specifically during the active eating period, particularly at dark onset when endogenous CORT levels normally peak and carbohydrate is exhibited as the preferred macronutrient.     

Acute, chronic, and interactive effects of type I and II corticosteroid receptor stimulation on feeding and weight gain

Type I (aldosterone) and/or type II (dexamethasone or RU28362) corticosterone receptor agonists were continuously infused in adrenalectomized Sprague-Dawley rats for 28 days at doses of 3.4, 17.2, or 86.2 nmol/day. Additional groups received combined agonist infusions, blank infusions, or sham operations. The type I agonist stimulated body weight gain, and the type II agonists were both suppressive, differing mainly in degree. Although there were a few early effects of these hormones (usually a stage of exaggerated activity), once passed, chronic stimulation was marked by steady or slightly increasing steroid influence on body weight. Throughout the chronic phase of this study there was no departure from a simple opponent model of type I and II ligand actions, and their combination approximated an arithmetic summation of the two separate agonists. This was generally true of feeding as well, although steroid effects on intake were always less pronounced. In contrast to chronic administration, acute combinations of these agonists were highly interactive, producing slight losses than large gains for the aldosterone and RU28362 combinations, but a large gain then small loss for the aldosterone and dexamethasone combination. These results imply that RU28362 and dexamethasone differ in more respects than potency. Because normal endogenous type II stimulation is acute and occurs against a background of type I receptor occupation, mixed agonist interactions are probably the rule for everyday physiological activity, not the exception.     

Excretion of electrolytes in Brown Norway and Fischer 344 rats: effects of adrenalectomy and of mineralocorticoid and glucocorticoid receptor ligands

Our previous studies showed that adrenalectomy (ADX) has surprisingly no effect on body weight and fluid intake in the Brown Norway rat strain, suggesting that mineralocorticoid receptor (MR)-mediated effects are present even in absence of corticosteroids in this strain. Moreover, glucocorticoid receptor (GR)-mediated mechanisms are more effective in Brown Norway than in Fischer 344 rats. Such functional differences in corticosteroid receptor pathways between Brown Norway and Fischer 344 rats led us to compare the effect of ADX and MR/GR-mediated actions on sodium and potassium excretion between these two rat strains. To this end, we first measured the effect of an acute high dose of aldosterone on the urinary Na+/K+ concentration ratio in intact and ADX Brown Norway and Fischer 344 rats. Second, to discriminate mineralocorticoid from glucocorticoid actions, we treated chronically ADX rats with increasing doses of aldosterone or RU28362, a pure GR agonist, in the drinking fluid. As sodium homeostasis involves salt appetite regulation, behaviour under mineralocorticoid control, we also measured saline preference in Brown Norway and Fischer 344 rats. Our data illustrate: (1) the very limited effect of ADX on body weight, food and fluid intake, diuresis, natriuresis, kaliuresis and salt appetite in Brown Norway rats, supporting the presence of MR signalling pathways in the absence of adrenal steroids in these rats; (2) the insensitivity of MR to aldosterone in intact Brown Norway rats, and the reduced sensitivity of MR to aldosterone in ADX Brown Norway rats compared with ADX Fischer 344 rats; and (3) the greater sensitivity of GR-related mechanisms to RU28362 in Brown Norway than in Fischer 344 rats in terms of body weight gain and electrolyte excretion. Considering that both MRs and GRs regulate hypothalamic-pituitary-adrenal axis processes, such functional differences in corticosteroid receptors could be at the origin, at least partly, of the strain differences in corticotropic activity/reactivity to stress previously described.     

The effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence in rats

The present study examined the effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence (BSS) in rats. The 5-HT1A receptor agonist, 8-OH-DPAT (0.5 microg), and the 5-HT2C receptor agonist, Ro-60-0175 (3.0 microg), were injected into the paraventricular nucleus (PVN) of rats. The animals were maintained on an ad libitum feeding paradigm with access to water and individual sources of protein, carbohydrate, and fat. Intra-PVN administration of each agonist was associated with decreased carbohydrate consumption. The effect was enhanced by the administration of both agonists together. Behavioral analysis indicated that co-administration of 8-OH-DPAT and Ro-60-0175 interrupted the natural BSS with an increase in non-feeding behavior, whereas the 8-OH-DPAT alone promoted early development of the natural BSS. In conclusion, the 5-HT receptor agonists affected serotonergic modulation of feeding behavior in a functionally selective way.     

Effects of adrenalectomy and hormone replacement on B6C3F1 mice fed a high-fat diet

Bilateral adrenalectomy (ADX) causes decreased circulating leptin in both obese and lean mice. It remains unclear whether the decreased plasma leptin after ADX is due to decreased adipose tissue or is due to decreased circulating glucocorticoids. The present experiment was performed to test the hypothesis that the absence of glucocorticoids from circulation is sufficient to decrease circulating leptin. Sixty-four adult male B6C3F1 mice were individually housed and fed either Purina rat chow or an experimental diet. After 6 weeks, mice fed the experimental diet gained more weight than mice fed the control diet. Each dietary group was then subdivided into four groups: ADX with cholesterol replacement (ADX-CHOL), ADX with corticosterone (CORT) replacement (ADX+CORT), ADX with aldosterone (ALDO) replacement (ADX+ALDO), and sham operation (SHAM). Two days after surgery, mice were killed and exsanguinated and the carcasses were prepared for gravimetric analyses. Blood was collected and centrifuged and the plasma was assayed for leptin, CORT, and ALDO. Blood glucose was determined using whole blood taken before centrifugation. There was no difference in body weight due to ADX after 2 days. Mice fed the experimental diet had higher circulating leptin than those fed the control diet. The ADX+CORT groups (both experimental and control diets) had higher plasma leptin concentrations than the other groups. No differences were observed between ADX-CHOL and SHAM groups. These results suggest that circulating leptin is not directly controlled by glucocorticoids. The effect of ADX on circulating leptin reported by others may be the consequence of decreased adiposity.     

The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor

Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3F1 mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found.     

Central administration of ghrelin preferentially enhances fat ingestion

Ghrelin, a brain-gut peptide discovered from the stomach, stimulates growth hormone release, food intake, adiposity, and weight gain. Circulating ghrelin levels are modulated under conditions of positive and negative energy balance, however its effect on macronutrient selection is not known. The present experiment investigates the effect of ghrelin on single and two-diet feeding paradigms in high-carbohydrate (HC) and high-fat (HF) preferring rats. In the macronutrient selection test in which rats were given free access to either high-carbohydrate or high-fat diet, an intracerebroventricular (i.c.v.) administration of ghrelin potently enhanced fat intake over carbohydrate intake in both HC- and HF-preferring rats. In the diet preference test in which rats were given free access to both high-carbohydrate and high-fat diets simultaneously, an i.c.v. administration of ghrelin also preferentially enhanced fat consumption over carbohydrate in both HF- and HC-preferring rats. Intracerebroventricular administrations of galanin and neuropeptide Y enhanced fat and carbohydrate ingestion, respectively. Centrally administered ghrelin enhanced fat ingestion. These results provide further insights for the role of ghrelin in feeding behavior and the development of obesity.     

Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic–pituitary–adrenal axis via estrogen receptor alpha within the hypothalamus

Numerous studies have established a link between individuals with affective disorders and a dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, most notably characterized by a reduced sensitivity to glucocorticoid negative (−) feedback. Furthermore there is a sex difference in the etiology of mood disorders with incidence in females being two to three times that of males, an association that may be a result of the influence of estradiol (E2) on HPA axis function. In these studies, we have examined the effect of E2 on glucocorticoid-mediated HPA axis (−) feedback during both the diurnal peak and the stress-induced rise in corticosterone (CORT). Young adult female Sprague–Dawley (SD) rats were ovariectomized (OVX) and 1 week later treated subcutaneous (s.c.) with oil or estradiol benzoate (EB) for 4 days. On the 4th day of treatment, animals were injected with a single dose of dexamethasone (DEX), or vehicle. EB treatment significantly increased the evening elevation in CORT and the stress-induced rise in CORT. In contrast, DEX treatment reduced the diurnal and stress induced rise in CORT and adrenocorticotropic hormone (ACTH), and this reduction was not apparent following co-treatment with EB. To determine a potential site of E2's action, female SD rats were OVX and 1 week later, wax pellets containing E2, the estrogen receptor beta (ERβ) agonist diarylpropionitrile (DPN), or the estrogen receptor alpha (ERα) agonist propylpyrazoletriol (PPT), was implanted bilaterally and dorsal to the paraventricular nucleus of the hypothalamus (PVN). Seven days later, animals were injected s.c. with a single dose of DEX, or vehicle to test for glucocorticoid-dependent (−) feedback. Results show that E2 and PPT increased, while DPN decreased the diurnal peak and stress-induced CORT and ACTH levels as compared to controls. Furthermore, E2 and PPT impaired the ability of DEX to inhibit both the diurnal and the stress-induced rise in CORT and ACTH, whereas DPN had no effect. Neuronal activation was measured by c-fos mRNA expression within the PVN following restraint. E2 and PPT increased c-fos mRNA, and impaired the normal DEX suppression of neuronal activation in the PVN. Taken together, these data indicate that estradiol causes a dysregulation of HPA axis (−) feedback as evidenced by the inability of DEX to suppress diurnal and stress-induced CORT and ACTH secretion. Additionally, the ability of E2 to inhibit glucocorticoid (–) feedback occurs specifically via ERα acting at the level of the PVN.     

Limited brain diffusion of the glucocorticoid receptor agonist RU28362 following i.c.v. administration: implications for i.c.v. drug delivery and glucocorticoid negative feedback in the hypothalamic-pituitary-adrenal axis

The experiments described herein present a method for tracking diffusion of the glucocorticoid receptor agonist RU28362 in brain following i.c.v. drug administration. A useful property of glucocorticoid receptor is that it is primarily cytoplasmic when unbound and rapidly translocates to the nucleus when bound by ligand. Thus, removal of endogenous glucocorticoids by adrenalectomy allows us to identify brain regions with activated glucocorticoid receptor after i.c.v. glucocorticoid receptor agonist treatment by examining the presence or absence of nuclear glucocorticoid receptor immunostaining. We have previously demonstrated that an i.p. injection of 150 microg/kg RU28362 1 h prior to restraint stress is sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis hormone secretion [Ginsberg AB, Campeau S, Day HE, Spencer RL (2003) Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis hormone secretion and expression of corticotropin-releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 15:1075-1083]. We report here, however, that in rats i.c.v. treatment with a high-dose of RU28362 (1 microg) 1 h prior to stressor onset does not suppress stress-induced hypothalamic-pituitary-adrenal axis activity. We then performed a series of experiments to examine the possible differences in glucocorticoid receptor activation patterns in brain and pituitary after i.c.v. or i.p. treatment with RU28362. In a dose-response study we found that 1 h after i.c.v. injection of RU28362 (0.001, 0.1 and 1.0 microg) glucocorticoid receptor nuclear immunoreactivity was only evident in brain tissue immediately adjacent to the lateral or third ventricle, including the medial but not more lateral portion of the medial parvocellular paraventricular nucleus of the hypothalamus. In contrast, i.p. injection of RU28362 produced a uniform predominantly nuclear glucocorticoid receptor immunostaining pattern throughout all brain tissue. I.c.v. injection of the endogenous glucocorticoid receptor agonist, corticosterone (1 microg) also had limited diffusion into brain tissue. Time-course studies indicated that there was not a greater extent of nuclear glucocorticoid receptor immunostaining present in brain after shorter (10 or 30 min) or longer (2 or 3 h) intervals of time after i.c.v. RU28362 injection. Importantly, time-course studies found that i.c.v. RU28362 produced significant increases in nuclear glucocorticoid receptor immunostaining in the anterior pituitary that were evident within 10 min after injection and maximal after 1 h. These studies support an extensive literature indicating that drugs have very limited ability to diffuse out of the ventricles into brain tissue after i.c.v. injection, while at the same time reaching peripheral tissue sites. In addition, these studies indicate that significant occupancy of some glucocorticoid receptor within the paraventricular nucleus of the hypothalamus and pituitary is not necessarily sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis activity.     

Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions

Noradrenergic mechanisms of the hypothalamic paraventricular nucleus (PVN) have been shown to play an important role in the stimulation of feeding To determine the influence of this nucleus in monitoring and controlling responses to physiological and pharmacological challenges, PVN electrolytic lesion rats were tested for their behavioral responsiveness to agents known to affect the alpha-2 noradrenergic system as well as release of corticosterone, and to short- and long-term periods of food deprivation. Discrete lesions of the PVN produced enhanced feeding, particularly of carbohydrate, in freely-feeding rats maintained on a macronutrient self-selection paradigm. Lesion rats demonstrated a behavioral deficit in food intake regulation (a decrease in carbohydrate ingestion) in response to 5-hr and 24-hr fasts, showed a disturbance in circadian feeding, and exhibited a dramatic decrease in circulating corticosterone. However, feeding in response to 2-deoxy-D-glucose and insulin remained intact, suggesting that noradrenergic receptors within the PVN are not involved in the mediation of glucoprivic-induced feeding.     

Adrenalectomy abolishes fasting-induced down-regulation of NADPH-diaphorase in the rat paraventricular nucleus

This study was conducted to define the molecular mechanism of fasting-induced down-regulation of neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN). Rats were adrenalectomized (ADX), and then either underwent food deprivation or received varying doses of dexamethasone for 48 h. The brain tissues were processed for NADPH-diaphorase (NADPH-d) staining, a histochemical marker of nNOS enzyme activity. Both the ADX and the sham operated rats showed a significant weight loss after 48 h of food deprivation. Food deprivation decreased the number of NADPH-d containing cells in the PVN of sham rats, however, not in the ADX rats. Dexamethasone dose- dependently decreased NADPH-d cells in the PVN of ADX rats. The effect of ADX or dexamethasone was limited to the parvocellular subdivision of PVN. These results suggest that the adrenal glucocorticoids may down-regulate nNOS expression in the PVN during food deprivation.     

Galanin in the PVN increases nutrient intake and changes peripheral hormone levels in the rat

In self-selection feeding paradigms, rats display differential patterns of nutrient (protein, carbohydrate or fat) intake. Factors known to influence this selection include brain peptides as well as circadian parameters. In this series of experiments we investigated the role of PVN galanin in nutrient intake during the early and late dark periods in the rat. Rats were allowed to select between three isocaloric diets enriched in protein, carbohydrate or fat. Following a 2-week adaptation period, the animals' 24-h intake was monitored for 4 weeks. Galanin was injected into the PVN and food intake was measured 1, 2 and 24 h post-injection. Galanin significantly increased the 1 h total food intake but it failed to increase the intake of any particular nutrient. Galanin had no effect 2 or 24 h post-injection. Analysis of the data grouped by preference based on the rats 24 h baseline selection patterns over the 4-week period revealed that galanin seem to increase the preferred nutrient. That is, galanin preferentially increased the intake of the carbohydrate- or fat-rich diet in animals with high (over 40% of the total food intake) 24-h baselines in this particular nutrient. Finally, analysis of the plasma hormone levels after paraventricular galanin administration revealed a significant increase in noradrenaline levels, a small reduction in plasma insulin with no effects on adrenaline, glucose or corticosterone. The data revealed that galanin in the PVN influences both food intake and metabolic functioning. PVN galanin significantly increases sympathetic outflow and seems to stimulate the intake of the individual rat's preferred macronutrient.     

Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone

The function of the second nuclear estrogen receptor, estrogen receptor beta (ERbeta), in the brain is largely unknown. The present study tested whether 1) ERbeta in the paraventricular nucleus (PVN) of the hypothalamus has a direct role in the hypothalamic-pituitary-adrenal (HPA) axis-mediated stress function, and 2) whether corticosterone (CORT) can regulate ERbeta gene expression in the PVN in the intact, cycling female rat. To test the first hypothesis a pure estrogen receptor antagonist, ICI182, 780, was microinjected into the PVN bilaterally and stress-induced CORT response to an acute stressor (15 min restraint) was measured at 0, 15, 30, 60 and 90 min time points. Estrogen antagonist-injected rats showed inhibited CORT levels at the peak (15 min) of the stress response compared with vehicle-injected animals. To test the second hypothesis, ERbeta mRNA levels were measured in the PVN using in situ hybridization histochemistry following sham surgery, adrenalectomy, and adrenalectomy with low or high CORT replacement. Adrenalectomy reduced ERbeta mRNA expression in the PVN, whereas CORT replacement fully reversed this effect in a dose-dependent fashion. Both antagonist inhibition of CORT response and CORT-mediated regulation of ERbeta mRNA were found to be estrus cycle-dependent in the intact, cycling female. These data suggest that ERbeta in the PVN may critically modulate the HPA axis response to stress and is, in turn, regulated by circulating CORT.     

Structure-function analysis of stimulation of food intake by neuropeptide Y: effects of receptor agonists.

Neuropeptide Y (NPY) is a potent natural orexigenic signal in the rat. In this study, we have compared the effects of several COOH-terminal fragments of NPY and NPY receptor agonists on cumulative food intake in male rats. Rats were implanted with permanent cannulae either into the third cerebroventricle or paraventricular nucleus (PVN). NPY1-36 and various COOH-terminal fragments of NPY, two agonist analogues [Leu31, Pro34]NPY and NPY 1-4-Aca (epsilon-amino-caproic acid)-25-36, were administered intracerebroventricularly (ICV) or directly into the PVN, and the cumulative 2-h food intake response was compared. We observed that peptides that were effective by ICV were also effective when administered into the PVN, but smaller amounts of the peptides were required after PVN injection to evoke an equivalent food intake response. Injection of NPY1-36 induced a dose-dependent increment in food intake. Surprisingly, deletion of NH2-terminal tyrosine residue did not adversely affect feeding behavior. In fact, NPY2-36 was consistently more effective than NPY1-36; the enhancement in feeding by NPY2-36 was dose-related and was higher than evoked by NPY1-36 at each dose tested. Further serial deletion of aminoacids at NH2-terminal resulted in complete loss of activity. In addition, NPY agonist analogue, NPY 1-4-Aca-25-36, failed to stimulate feeding. However, NPY Y1 receptor agonist, [Leu31, Pro34]NPY, but not Y2 receptor agonist, NPY13-36, stimulated feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the glucocorticoid milieu on the immunostaining of peptide histidine isoleucine (PHI) in the rat hypothalamus

Effects of adrenalectomy (ADX) or dexamethasone (DEX) treatment on the immunostaining of hypothalamic peptide histidine isoleucine (PHI) were examined in male rats. After colchicine treatment, PHI-containing cell bodies were observed in the suprachiasmatic nucleus (SCN) and the parvocellular division of the paraventricular nucleus (PVN). ADX increased and DEX dose-dependently decreased the number of PHI-immunopositive neurons in the PVN. The number of SCN-PHI neurons was not affected by any treatment employed in this study. These results suggest that PVN-PHI neurons are under the effects of the glucocorticoid milieu, and that the neurons may be involved in the glucocorticoid regulation of adrenocorticotropin and prolactin secretion.     

Role of cannabinoid CB1 receptors on macronutrient selection and satiety in rats

It has been shown that endogenous and exogenous cannabinoids substantially increase feeding. Despite evidence for a role of endocannabinoids in mediating food ingestion, the mechanisms by which CB1 receptor agonists and antagonists have an effect on motivational processes (hunger, satiety) as well as on specific food preference are not entirely understood. The purpose of this study was to investigate the effects of systemic injection of the CB1 receptor agonist, ACEA, on protein, carbohydrates and fat intake as well as on the behavioural satiety sequence (BSS) in pre-satiated rats. Following a 120-min access to a three pure nutrient diet (protein, carbohydrates and fat) at dark onset, male Wistar rats were injected intraperitoneally with ACEA (0.1, 0.25, 0.5 and 1.0 mg/kg). Immediately after the injection, animals were placed into separate experimental cages with free access to food and a single 60-min period was video recorded to evaluate the BSS; protein, carbohydrates and fat intake (g) was measured at the same period of time. Intake of carbohydrates was significantly increased and this effect was prevented by the pre-treatment with AM 251. Analysis of BSS showed that administration of 0.5 mg/kg of ACEA reversed the satiation induced by food ingestion by increasing the time spent eating and decreasing the time resting without altering the overall activity. The present results suggest that the stimulation of food intake induced by activation of CB1 receptors involves a specific dietary component and behavioural selective mechanisms (stimulating hunger and inhibiting satiety).     

Effects of adrenalectomy and deprivation condition on food intake after phenylpropanolamine or clonidine.

alpha-Adrenergic receptors within the paraventricular hypothalamus (PVN) modulate feeding such that activation of alpha 2-adrenoceptors by drugs such as clonidine (CLON) increase feeding; whereas activation of alpha 1-adrenoceptors by drugs such as phenylpropanolamine (PPA) suppress feeding. Prior studies suggest that the feeding-stimulatory effect of alpha 2-adrenergic activation is a function of drug dose as well as the deprivation condition and adrenal status of the animal. Specifically, CLON's effects on feeding are greatest at low doses in food-satiated adrenally intact rats. Whether a similar profile is produced by alpha 1-adrenoceptor agonists such as PPA has not previously been explored. Thus, the present study provides a comparison of the effects on food intake of drug dose, deprivation condition, and adrenalectomy induced by these alpha 2- and alpha 1-adrenergic drugs. Accordingly, both adrenalectomized (ADX) as well as sham-control (SHAM) adult male rats underwent a series of 1-h feeding tests following administration of PPA (5, 10, 20 mg/kg, IP) as well as CLON (0.0125, 0.025, 0.05, 0.1 mg/kg, IP) under both deprived and nondeprived testing conditions. The results suggest that the deprivation condition, but not the surgical condition (ADX vs. SHAM), exerts the greatest overall effect on food intake following administration of alpha-adrenergic drugs.     

Noradrenaline-induced feeding responses in the rat do not depend on food characteristics

The noradrenergic system of the hypothalamic paraventricular nuclei (PVN) has been associated with feeding, but whether it controls feeding in a way that is relevant to energy balance is still unclear. Rats were maintained on a high energy, carbohydrate-rich diet (HC) or a low energy, carbohydrate-free, protein-rich diet (LP) until their daily energy intakes equalized. When injected with noradrenaline (NA) into the PVN, they ingested the same amounts of both diets so that the animals on the LP diet consumed only half the total energy of those on the HC diet. Continuous delivery of NA into the PVN via a microdialysis probe induced chewing on non-nutritive pieces of corks. The same chewing pattern could again be elicited by the subsequent NA deliveries. It is concluded that the nutritional value of a diet is irrelevant to the NA feeding response. The failure of NA administration to increase rat feeding in terms of energy intake, combined with its ability to stimulate chewing, suggests that the primary role of the NA system of the PVN may not be controlling the carbohydrate and energy intake, but rather gating behavioral responses that under appropriate circumstances may lead to ingestion.     

Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake

Valine-proline-aspartate-proline-arginine (VPDPR), the amino terminal pentapeptide of pancreatic procolipase, produced a dose-dependent reduction in food intake when injected intraperitoneally into Osborne-Mendel rats that had been starved overnight. This inhibition of feeding was observed when the rats were fed a high-fat diet but not in rats fed a high-carbohydrate, low-fat diet. At higher doses of VPDPR, the inhibition of feeding was maintained for over 6 hours. An equimolar mixture of the free amino acids had no effect on food intake. In rats adapted to a three-choice macronutrient diet, VPDPR inhibited fat intake but had no effect on carbohydrate or protein intake. This selective inhibition of fat intake was observed in both overnight-fasted rats presented with food and in ad-lib-fed rats at the beginning of the dark-onset feeding period. It is suggested that this peptide may be a feedback signal to regulate the intake of dietary fat.