Independent effects of estradiol on water and food intake.

Conducted 6 experiments to examine the effects of estradiol on ingestive behaviors of guinea pigs. Estradiol treatment was found to reduce water intake independently of its actions on food intake and body weight. In the 1st experiment, minimum intake and body weight of 17 intact female guinea pigs coincided with rupture of the vaginal membrane, the estimated time of ovulation. In Exp II, injections of 3 μg of estradiol benzoate (EB)/day to 7 ovariectomized females significantly depressed food intake, water intake, and body weight, compared with 7 Ss that received oil injections. Reducing food rations to 30% below ad lib levels in Exp III by itself had no significant effect on drinking in ovariectomized Ss. In Exp IV, therefore, ovariectomized females were first placed on a food ration 30% below ad lib levels and then injected daily with either 3 μg of EB or oil. Compared with oil injections, these EB injections significantly reduced water intake, while food intake did not decline significantly. Findings indicate that estradiol operates through different mechanisms to affect water intake and food intake. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat.

In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose-dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential migration of Th1 and Th2 cells--implications for vaccine and infection studies

We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 microg/kg) and sulfated CCK-8 (3.5 microg/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0. 3-fold respectively). Injections of leptin-CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin-CCK to regulate food intake.     

Functional mapping of neural sites mediating prolactin-induced hyperphagia in doves

Microinjections of prolactin (PRL) into the ventromedial nucleus of the hypothalamus (VMN) or the preoptic area (POA) have been previously shown to increase food intake and body weight in ring doves. In an attempt to corroborate these results and to provide a more complete map of PRL-sensitive brain sites mediating the orexigenic action of PRL, a microinjection procedure was employed in the present study that delivered PRL or saline vehicle in extremely small volumes (10 nl/injection) to a variety of diencephalic sites in dove brain that had been previously demonstrated to contain high concentrations of PRL receptors. Estimates obtained from one female subject given a single 10 nl injection of [125I]ovine PRL into the VMN supported the claim that such injection volumes resulted in limited diffusion, as 80% of the tissue radioactivity was found within a 280 mm area surrounding the injection site at 30 min after injection. Food intake of cannulated male doves in the mapping study was monitored daily during a 6 day baseline period, an initial 4 day treatment period, a 6-12 day post-treatment recovery period, and a second 4 day treatment period. Approximately half of the birds received PRL injections (50 ng/10 nl twice daily) and saine vehicle injections (10 nl twice daily) during the first and second treatment periods, respectively, while remaining birds received these treatments in the reverse order. No significant changes in food intake across baseline, vehicle, post-treatment, or PRL treatment periods were observed in birds with injection sites in the lateral POA, paraventricular nucleus of the hypothalamus (PVN), or the medial-basal hypothalamic region between the tuberal hypothalamus (TU) and VMN. In contrast, injections of PRL into the VMN area, medial POA, or TU resulted in average daily food intake values that significantly exceeded those recorded during other periods. The most robust feeding response was seen in the VMN group, where PRL injections resulted in a 58% increase in food intake over that recorded during injection of vehicle. This increase was significantly greater than that observed following PRL injections into the mPOA (26%) or the TU (32%). These findings suggest that the VMN may be a primary site of PRL action in promoting hyperphagia in this species, although PRL effects at other diencephalic loci, such as the mPOA and TU, may also contribute to the orexigenic action of this hormone.     

Thyroxine treatment reduces the anorectic effect of estradiol in rats.

Examined a possible interaction between thyroxine and estradiol in the control of feeding in female Sprague-Dawley rats. 14 ovariectomized Ss were given daily injections of 9.8 μg/100 g of body weight of 1-thyroxine (TX). Another 14 Ss received 0.15 ml of saline (SAL) subcutaneously each day, and food intake was measured for both groups daily. After 15 days of treatment, 8 Ss from each group were also given a single injection of 6 μg of estradiol benzoate (EB), and the remaining 6 Ss of each group received peanut oil vehicle. It was found that TX-treated Ss showed a significantly smaller drop in food intake after EB than did SAL-treated Ss. This TX-induced decrease in responsiveness to EB may be related to effects of TX on general metabolism. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Ovariectomized female hamsters received small unilateral implants of estradiol at a variety of anterior-posterior levels of the medial preoptic area and hypothalamus. The results of an initial experiment using 27-ga. implants showed that females with estradiol implants in the ventromedial hypothalamus (VMN) or nearby anterior hypothalamus consistently showed higher levels of sexual receptivity than did females with implants farther rostral, in the preoptic area, or farther caudal, in the posterior hypothalamus. A second experiment used smaller, 28-ga. implants to compare directly the two areas at which implants were effective in the first experiment. The results confirm the findings of other recent studies of hamsters and rats by identifying the VMN as the most effective hypothalamic site for the estrogen priming of sexual receptivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food for thought: a critique on the hypothesis that endogenous cholecystokinin acts as a physiological satiety factor

This review evaluates the various lines of evidence supporting the hypothesis that cholecystokinin (CCK) released from the small intestine during feeding plays a physiological satiety. Issues considered include, the effects of systemic injection of CCK on consummatory and operant feeding, the role of the vagus nerve, the effects of CCKB receptor antagonists, and the neuroendocrine responses to exogenous CCK. A critical appraisal of this research indicates that while it is clearly demonstratable that exogenous peripheral CCK can alter food intake by acting on CCKA receptors, the mechanism involved may be more closely related to the induction if aversion and nausea, rather than satiety. With regard to peripheral endogenous CCK, the available evidence also does not seem to support a role for the hormone in satiety. In particular, it is doubtful whether plasma concentrations of CCK following a meal are sufficiently high to inhibit feeding. Moreover, CCKA receptor antagonist which do not cross the blood brain barrier fail to increase meal size, as would be expected if peripheral CCK was an effective satiety factor. In addition, the recent literature concerned with the possibility that CCK may have a direct action within the brain in the control of food intake has been reviewed. These studies show that CCK administered intracerebroventicularly, or by micoinjection into discrete brain regions, also inhibits feeding via a CCKA receptor mechanism. However, the physiological relevance of these findings have yet to be determined.     

Effects of putative satiety peptides on feeding and drinking behavior in golden hamsters (Mesocricetus auratus).

Intraperitoneal cholecystokinin octapeptide (CCK-8 [0.1–5 μg/kg]) reduced feeding in Syrian hamsters in a dose-related fashion, except for males tested during the light phase of the illumination cycle. Proglumide (200 or 400 mg/kg), a putative CCK receptor antagonist, did not alter spontaneous food intake and did not reverse the suppression of feeding resulting from CCK-8. Bombesin (BBS [0.5–20 μg/kg]), thyrotropin releasing hormone (TRH [5–200 μg/kg]), and calcitonin (CC [2–22 μg/kg]) produced a dose-related suppression of food intake. BBS appeared to do so specifically. In contrast, TRH appeared to reduce feeding by temporarily debilitating the Ss and CC by evoking behavior (increased locomotor activity) incompatible with feeding. Intracerebroventricular (icv) injections of CCK-8, BBS, and CC produced dose-related inhibition of feeding, but only CCK-8 appeared to affect feeding behavior selectively. Reduced feeding after icv BBS was associated with excessive grooming, and icv CC, like systemic CC, increased locomotor behavior. (72 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of cholecystokinin in the motivational control of instrumental action in rats.

In 4 experiments, the role of cholecystokinin (CCK) in the motivational control of instrumental performance in rats was assessed. Following instrumental training with food rewards, injections of CCK (either 2 μg/kg or 4 μg/kg) had no effect on instrumental performance in extinction, even when the opportunity was given to learn about the incentive value of the food outcome under CCK. These results contrasted markedly with the effects of shifts in food deprivation. Rewarded instrumental performance was, however, reduced by both doses of CCK, suggesting that CCK may mediate deprivation-related shifts in incentive value. Tests of this hypothesis found that the alimentary CCK antagonist devazepide (MK329) attenuated the devaluation of a food outcome produced by exposure to the outcome in a nondeprived state. These data are interpreted as suggesting that CCK may act as a satiety-specific incentive signal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Variation of food intake and body weight with estrous cycle, ovariectomy, and estradiol benzoate treatment in hamsters (Mesocricetus auratus).

In 3 experiments with 46 female hamsters, food intake and body weight fluctuated systematically with the estrous cycle. Food intake and body weight were lowest when elevated endogenous estrogen levels were expected. Ovariectomized Ss gained a significant amount of body weight compared with sham-operated Ss. Replacement therapy with estradiol benzoate reduced the body weight and food intake of ovariectomized Ss relative to oil-injected, ovariectomized controls. Results are compared with similar data from rats; they support the concept that in females of both species estradiol operates to regulate food intake and body weight. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes

Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.     

Effects of hysterectomy on sexual receptivity, food intake, running wheel activity, and hypothalamic estrogen and progestin receptors in rats.

Ovariectomized-hysterectomized (OH) CD rats given sequential treatments with 2 μg of estradiol benzoate (EB) and .5 mg of progesterone (P) showed significantly higher lordosis quotients than ovariectomized (OV) Ss in 2 tests, 1 and 2 wks after surgery. To test whether the effects of hysterectomy persist, 3 groups of OV and OH Ss received weekly injections of EB, EB?+?P, or sesame oil for 4 wks, were given 2 μg of EB followed 24 hrs later by .5 mg of P, and tested for receptivity. Only the OH Ss that had received hormones for 4 wks showed a significantly higher lordosis score than OV Ss. The effects of hysterectomy on food intake, weight gain, and running wheel activity were also tested. After 1 wk of 2 μg/day EB, OH Ss lost significantly more weight and consumed less food than OV Ss, but by 2 wks the effects of hysterectomy were no longer evident. Treatment with .5 μg/day EB resulted in a significant loss in weight and food intake in OH Ss throughout the experiment. OH Ss implanted with Silastic capsules containing EB were significantly more active in running wheels than OV Ss over the 1st 9 days, but by Day 23 the activity of both groups was similar. 24 hrs following a single injection of EB, hypothalamic-preoptic area cell nuclear estrogen receptors and cytoplasmic progestin receptors were significantly higher in OH than in OV Ss. Possible mechanisms by which hysterectomy might act to enhance hormone-dependent behaviors are discussed. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dietary variety, energy regulation, and obesity.

Increased variety in the food supply may contribute to the development and maintenance of obesity. Thirty-nine studies examining dietary variety, energy intake, and body composition are reviewed. Animal and human studies show that food consumption increases when there is more variety in a meal or diet and that greater dietary variety is associated with increased body weight and fat. A hypothesized mechanism for these findings is sensory-specific satiety, a phenomenon demonstrating greater reductions in hedonic ratings or intake of foods consumed compared with foods not consumed. Nineteen studies documenting change in preference, intake, and hedonic ratings of food after a food has been eaten to satiation in animals and humans are reviewed, and the theory of sensory-specific satiety is examined. The review concludes with the relevance of oral habituation theory as a unifying construct for the effects of variety of sensory-specific satiety, clinical implications of dietary variety and sensory-specific satiety on energy regulation, and suggestions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of centrally administered CCK-receptor antagonists on food intake in rats

Cholecystokinin (CCK) receptors are classified as two subtypes, designated CCK(A) and CCK(B), and both subtypes are found in brain and peripheral tissues of rats. CCK-8 has been shown to act peripherally to reduce meal size, and this satiating action can be blocked by CCK(A)-receptor antagonists. Recent evidence suggests that, in addition to the peripheral action of CCK, central CCK mechanisms may also be involved in satiety. Central administration of proglumide, a mixed CCK-receptor antagonist (CCK(A) > CCK(B)) has been shown to increase food intake and block the satiating effect of peripherally administered CCK-8 (15). In an attempt to replicate and extend these results, rats were given injections of proglumide or selective CCK-receptor antagonists into the lateral ventricle prior to a peripheral injection of CCK-8 or saline. Only proglumide stimulated an increase in 30-min test meal intake and attenuated the satiating effect of CCK-8. Two selective CCK(A)-receptor antagonists, lorglumide and devazepide, did not increase intake significantly when given alone, and they did not attenuate the effect of peripherally administered CCK-8. The selective CCK(B)-receptor antagonist, L365,260, reduced intake at all doses tested except the lowest. The lowest dose did not increase intake when given alone and did not attenuate the inhibitory effect of CCK on test-meal intake. Finally, a combination of devazepide and L365,260 did not increase intake or block the effect of peripherally administered CCK-8. These results suggest that CCK released by neurons in the brain and acting on central CCK(A)- and CCK(B)-receptors is not necessary for the control of meal size or for the satiating effect of peripherally administered CCK-8 in rats under our experimental conditions.     

Origin of endocrine-metabolic changes in the weanling rat ventromedial syndrome

Destruction of the ventromedial hypothalamic nuclei (VMN) in the weanling rat without injury to the median eminence results in a series of somatic, endocrine, and metabolic changes that are characterized by normal food and water intake but decreased linear growth, normal body weight but increased carcass fat and reduced carcass protein, lean body mass, and water. The endocrine alterations comprise hyperinsulinemia in the face of normoglycemia, hypertriglyceridemia and hypercholesterolemia and reduced growth hormone levels. The metabolic changes include greater oxidation of glucose and incorporation into lipid and reduced palmitate oxidation but increased incorporation into lipid. Weanling rats with VMN lesions are normophagic in absolute terms, relative to body weight and per metabolic unit, but their nocturnal feeding and weight gain cycles are disrupted and their locomotor activity is reduced. The VMN are involved in the long-term control of feeding - as in the mature rat - as shown by intragastric preloading studies and dietary density manipulation, glucose preference tests and intraperitoneal injections with glucose. Hyperinsulinemia and hypertriglyceridemia are present four days after the VMN operation in the presence of subnormal food intake and plasma glucose levels. Manipulations of the fat content of the diet revealed that the hyperlipidemia is of both endogenous and exogenous origin and that lipoprotein lipase is increased; a 48-hour fast reduced the hyperlipidemia to control levels, however. This suggests that weanling VMN rat tissue may have an impaired ability to take up circulating lipid. An increased incorporation of glycerol into lipid may be due to induction of glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed neither depressed lipolysis nor diminished lipolytic activity per milligram of tissue protein. Glucose oxidation and incorporation into adipose tissue is increased in several tissues in vitro and there is enhanced glucose disappearance from plasma and incorporation into tissue lipids in vivo. These changes develop within a short time after lesion production and persist at least partially up to six months: glucose utilization in liver increases already four hours after the operation whereas it takes 72 hours to commence in adipose tissue. Insulin resistance is not apparent either in vivo or in vitro. The decreased growth hormone levels are not critical to the metabolic changes, nor is the hyperinsulinemia totally necessary. The metabolic changes also appear on several different types of diet and persist with fasting. The latter does not reduce insulin sensitivity of VMN rat tissues, wheras it does so in normal rats. Mature rats developed the same metabolic changes even in the absence of hyperphagia. The metabolic alterations can be blocked by pharmacologic doses of glucocorticoids, but are enhanced by the administration of estrogen...     

RAGE mRNA expression in the diabetic mouse kidney

Data are accumulating that insulin acting in the central nervous system is a physiological regulator of food intake and body weight, presumably via its effect in the hypothalamus. The present study investigated whether infusion of a small dose of insulin into two major hypothalamic insulin-binding areas also has an effect on diet selection and behavior. At the beginning of the dark period, rats received local bilateral infusions of 4 microU of insulin or vehicle during 34 min into the arcuate (ARC) or paraventricular (PVN) nucleus of the hypothalamus. Consumption of carbohydrate (C)-, protein (P)-, and fat (F)-enriched food and time spent on certain behaviors (drinking, resting, grooming, rearing, exploring/sniffing) were assessed during the first nocturnal hour. In addition, 21-h diet selection was assessed. The percentage contribution of macronutrients (C/P/F) to total energy content of the C-, P-, and F-enriched diets was 71.9/17.2/10.9, 45.8/43.4/10.8, and 47.1/17.5/35.4, respectively. During the first hour, infusion of insulin into the PVN increased grooming behavior compared to infusion of the vehicle. Although infusion of insulin had no effect on diet selection during the first hour, insulin infused in the ARC caused a reduction in F-enriched food consumption and total intake of F (as a macronutrient) over the 21-h period without altering total food intake. Infusion of a higher dose of insulin (10 microU) into the third ventricle had no effect on any of the assessed parameters. The data are explained to indicate that insulin (being an indicator of a positive energy balance) adjusts body weight homeostasis by modulating the preference for fat, at least at the level of the ARC, but not at the PVN.     

Paraventricular hypothalamic clonidine increases rather than decreases susceptibility to activity-based anorexia in the rat.

Anorexia has been related to reduced activity of the paraventricular hypothalamic (PVN) noradrenergic-feeding system. This study attempted to determine whether clonidine (an α2-adrenergic agonist) infused into the PVN reduced susceptibility to activity-based anorexia (ABA) in the rat. In Exp 1, clonidine (6 doses) was chronically infused into the PVN of male Sprague-Dawley rats. All animals were exposed to ABA (1.5 hrs/day food access; 22.5 hrs/day running wheel access) until a 25% body weight loss was reached. Dose-related increases in susceptibility to ABA and decreases in food intake were observed. In Exp 2, for which heavier animals and 3 doses of clonidine were used, no difference was found in food intake and wheel activity, but there was increased susceptibility to ABA. Chronic clonidine infused into the PVN does not produce hyperphagia and exacerbates rather than attenuates susceptibility to ABA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some effects of ovarian hormones on food intake and body weight in female rats.

Conducted 3 experiments with a total of 63 ovariectomized and 41 ovariectomized-adrenalectomized Sprague-Dawley rats in which ovarian steroids affected food intake and body weight. These effects were probably mediated by estradiol and progesterone, since these 2 hormones were more effective than their principal metabolites (estrone 5a-pregnane-3,20-dione, 5ai0regnane-3,20-dione, respectively) in altering the food intake and body weight of ovariectomized Ss. Estradiol seemed to affect food intake by lowering the set point about which body weight is regulated in a dose-dependent fashion. These actions of estradiol could be attenuated or completely blocked by concurrent injections of progesterone. Estradiol-treated ovariectomized Ss were far more responsive to the weight- and appetite-promoting actions of progesterone than were ovariectomized-adrenalectomized Ss, suggesting that the principal action of progesterone on energy balance may be to interfere with the effects of estradiol. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Variable and invariable DNA repeat characters revealed by taxonprint approach are useful for molecular systematics

BACKGROUND: Normally the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) interact to regulate food intake (FI), the product of meal number (MN) and meal size (MZ), by changes in neurotransmitters, mainly dopamine and serotonin. Change in LHA dopamine influences meal size; while in VMN, decreasing dopamine and increasing serotonin levels influence meal number. Whether this situation exists in early cancer anorexia was tested in a series of studies to examine the role of the hypothalamus in the pathogenesis of early cancer anorexia. MATERIALS AND METHODS: In experiment 1, male Fischer tumor-bearing (TB) rats and weight-matched controls had FI, MN, and MZ measured continuously via a computerized rat eater meter. At onset of anorexia, feeding patterns were measured. In experiment 2, the VMN was temporarily blocked with 0.32 microgram of colchicine in TB rats, while TB controls had an equal volume of intra-VMN saline, and changes in feeding patterns were measured. In experiment 3, changes in VMN dopamine and serotonin were measured via microdialysis at anorexia and after tumor resection. RESULTS: In experiment 1, with the onset of anorexia, food intake decreased significantly in TB rats, initially by a decrease in MN and then by a decrease in both MN and MZ. No change occurred in controls, suggesting that VMN versus LHA played a more significant role in mediation of cancer anorexia. In experiment 2, following VMN block, FI increased significantly in anorectic TB rats, achieved by an almost exclusive increase in MN with minimal change in MZ, thus supporting the role of the VMN in anorexia. In experiment 3, at the onset of anorexia, FI decreased significantly in TB rats versus controls. TB rats had a significant increase in VMN serotonin and a significant decrease in VMN dopamine. After tumor resection, food intake improved and high levels of serotonin normalized with no change in dopamine. CONCLUSION: Serotoninergic and dopaminergic systems are involved in the etiology of cancer anorexia. The changes in food intake are mediated via the VMN by a decrease in meal number.