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S P Grossman

Publications and source records attributed to S P Grossman.

At least 19 recordsLinked to original sources

Chronic intrahypothalamic insulin infusion in the rat: behavioral specificity.

This study examines whether chronic intrahypothalamic (IH) insulin infusions suppress body weight and food intake directly or via effects on water intake or activity. Insulin (15 microU/h) was infused into the ventromedial hypothalamic nucleus of rats for 1 week. If IH insulin infusions primarily suppress water intake, animals should consume less water during insulin infusion in the absence of food. In the first experiment in this study, rats food deprived during IH insulin infusion did not drink significantly less than during vehicle infusion. This implies that IH insulin affects water intake secondarily to its impact on food intake. Insulin might suppress food intake and body weight by decreasing overall activity levels, including activity involved in ingestive behavior. In the second experiment, rats' activity on a running wheel was measured during IH insulin and vehicle infusion; activity increased during insulin infusion compared to vehicle infusion. These findings suggest that insulin's effects on food intake and body weight are via a mechanism that does not appear to directly influence water intake, and does not reduce overall activity levels.

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Chronic intrahypothalamic infusions of insulin or insulin antibodies alter body weight and food intake in the rat.

In Experiment 1, one-week infusion of insulin (0.15, 1.5, or 15.0 microU/hr) into the ventromedial hypothalamus (VMH) of rats reduced body weight (BW) and nighttime food intake (FI). While 0.15 microU/h decreased daytime FI, 1.5 microU/h increased daytime FI and 15.0 microU/h left daytime FI unchanged. Total daily FI was decreased by the two highest doses. In Experiment 2, intra-VMH infusion of specific insulin antibodies (1.5 microUeq/h) increased BW and FI, while C-peptide antibodies were ineffective. In Experiment 3a, intracerebroventricular infusions of insulin failed to decrease FI and BW comparably to similar intrahypothalamic infusions. In Experiment 3b, intra-VMH insulin was infused via cannulae that bypassed the cerebral ventricles. The decrease in FI and BW was comparable to that observed when insulin was infused via cannulae that penetrated a ventricle. Histology from animals used in Experiments 1-3 indicates that optimum sites for insulin-induced changes in BW and FI in the hypothalamus lie in an area that includes portions of the paraventricular, arcuate, dorsomedial, and ventromedial nuclei.

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Water intake during chronic preoptic infusions of osmotically active or inert solutions.

To further elucidate the role of the lateral preoptic area (LPO) as an osmoreceptive region, rats received chronic infusions (2 weeks) of low volumes (0.5 microliters/h) solutions of hypertonic sodium chloride (NaCl; 0.16 M), hypertonic potassium chloride (KCl; 0.16 M), hypertonic (0.32 M) or hypotonic (0.16 M) mannitol, isotonic saline, or water delivered bilaterally via subcutaneous osmotic minipumps attached to intracranial cannulae. All cannulae terminated within the anterior hypothalamus-preoptic region. Hypertonic NaCl and KCl increased water intake over preinfusion levels in the majority of animals tested. However, the effects were variable, including some sizable increases as well as decreases. Hypertonic mannitol decreased daily water intake in 15 of 25 rats and produced essentially no change in the average intake of the group. Isotonic NaCl produced smaller increases and decreases, while water produced larger changes in individual rats, but neither solution had a significant effect on the average intake of the group. None of the infusates significantly altered food intake.

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Role of intrahypothalamic insulin in circadian patterns of food intake, activity, and body temperature.

These experiments examined the extent to which chronic intrahypothalamic (IH) insulin infusions that alter circadian patterns of food intake (FI) affect the regulation of other diurnally varying behavior in the rat. One-week IH insulin infusion (1.5 microU/hr) significantly decreases rats' night FI and increases day FI but does not alter the diurnal pattern of activity. Mean daily core temperature increased slightly but significantly during insulin infusion, the daily peak of the body temperature rhythm did not shift significantly, and the daily range of body temperature increased. IH insulin infusion in rats living in constant light and thus without circadian rhythm of FI led to significant decreases in FI and body weight. These data support the conclusion that IH insulin infusion alters food intake and body weight through a specific effect on a neural system that regulates food intake and body weight, and not by altering circadian rhythms.

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Non-predatory ingestive behaviors of the praying mantids Tenodera aridifolia sinensis (Sauss.) and Sphodromantis lineola (Burr.).

Praying mantids are thought to be so strictly predacious that, historically, carnivorousness has been used as a defining characteristics of the taxon Mantodea, and no data exist on other ingestive behaviors. We observed food- and water-deprived male and female Tenodera aridifolia sinensis (Sauss.) and Sphodromantis lineola (Burr.) in various situations and found that their ingestive behaviors are more variable than generally recognized. Both species regularly drink water in response to deprivation, the amount imbibed being correlated with the total (but not daily) percent of initial body weight lost. When presented with stimuli consisting of plastic beads of different reflective quality (shiny clear, opaque frosted, or matte black), lighted by a single direct light source, the shiny stimuli consistently elicited the most drinking-like behavior by the mantids. The preference was consistent, whether stimuli were presented together or singly. This suggests that visual cues can be used to identify water and are alone capable of maintaining drinking-like behavior. When S. lineola were presented with various stimuli, including diced apple and diced banana, in a five-way or a three-way choice test, mantids that chose a stimulus within the allotted time consistently ate the diced banana. When presented one of two stimuli differing only in odor (30 x 20 x 15 mm cloth bags filled with either plastic beads or banana), S. lineola did not attempt to eat the former, but 50% attempted to eat the bag of banana. Eating bouts were always preceded by antennae drumming in the direction of, or over the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

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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.

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Lesions of the MPO or AV3V: influences on fluid intake.

Electrolytic lesions in the MPO of rats had no significant effects on ad lib food and water intake, but impaired the drinking response to 1 M NaCl. Large MPO lesions also produced a persistent increase in plasma osmolality. In Experiment 2, we depleted neurons from the MPO of rats by iontophoretic application of the neurotoxin kainic acid (KA) which destroys nerve cell bodies without damage to fibers of passage. KA-induced neuron depletion in the MPO of rats significantly reduced the drinking response to 1.0 M saline, to 30% PG, and to 30 micrograms/kg isoproterenol. Ad lib water intake and drinking responses to food or water deprivation, to low concentrations (0.5 M) of hypertonic saline, to low concentrations (10% or 20%) of PG, and to systemic administration of 1.5 mg/kg angiotensin II were within the normal range. In Experiment 3, rats with electrolytic lesions that were strictly confined to the tissue immediately surrounding the wall of the anteroventral portion of the third ventricle (AV3V), without invading the MPO displayed normal ad lib food and water intake and plasma osmolality as well as drinking responses to water deprivation, hypertonic saline (0.5 or 1.0 M), angiotensin II (1.5 mg/kg) and isoproterenol (30 micrograms/kg).

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Depletion of neurons from preoptic area impairs drinking to various dipsogens.

We depleted neurons from the lateral preoptic region (LPO) of rats by iontophoretic application of the neurotoxin kainic acid (KA). Rats with KA-induced damage to LPO neurons drank less water than controls after subcutaneous (SC) administration of: (a) 5 ml of a 1.0 M saline solution or (b) 5 ml of a 30% polyethylene glycol (PG) solution. The drinking response to 1.5 mg/kg angiotensin II (AII) was significantly smaller than was that of controls 15 min but not 1 hour after the SC injection. The experimental animals drank as much water as controls under ad lib conditions and showed normal drinking responses to low concentrations of hypertonic saline (0.5 M) or PG (10% or 20%).

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The role of glucose, insulin and glucagon in the regulation of food intake and body weight.

Glucose and related pancreatic hormones play a major role in the metabolism of monogastric mammals yet their influence on hunger and/or satiety is, as yet, poorly understood. Glucose, insulin and glucagon rise during a meal and gradually decline to baseline levels shortly after a meal. A sudden drop in plasma glucose as well as insulin have been reported just prior to the onset of a meal but the functional significance of this is not yet clear. Systemic injections of glucose have no acute satiety effects but intraduodenal and intrahepatic infusions reduce food intake and free-feeding and deprived animals respectively. Treatments which decrease cellular glucose utilization directly (2-DG) or indirectly (insulin) increase food intake while exogenous glucagon (which produces hyperglycemia) decreases it. There is considerable evidence that some or all of these effects may be due to a direct central action of glucose, 2-DG, insulin, and glucagon on brain mechanisms concerned with the regulation of hunger and satiety although influences on peripheral "glucoreceptors" have been demonstrated as well. The functional significance of glucoprivic feeding is, however, questioned. The feeding response to 2-DG and related compounds is capricious, and its temporal course does not parallel the hyperglycemic reaction which presumably reflects cellular glucopenia. Moreover, numerous brain lesions which increase, decrease, or have no effect on ad lib intake and often have no effect on the response to deprivation have been shown to severely impair or abolish feeding responses to systemic injections of 2-DG that produce severe central as well as peripheral glucopenia. Feeding responses to insulin are intact after most of these lesions, suggesting that this hormone may influence food intake in a fundamentally different fashion. The mechanism of insulin action is not understood--the classic feeding response is obtained only with doses that are pharmacological when compared to normal plasma levels and there is increasing evidence that lower doses may have opposite, inhibitory effects on food intake and body weight. Relatively small doses of glucagon decrease food intake (although opposite facilitatory effects have been reported after even smaller doses) but the effect does not appear to be due to hepatic mobilization of glucose as initially assumed. Decreases in food intake after intracranial injections of very small doses suggest a direct central action.

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A reassessment of the brain mechanisms that control thirst.

The classic " hypothalamocentric " theory of thirst has increasingly been challenged because the effects of hypothalamic lesions are not as behaviorally or anatomically specific as earlier research indicated. Instead, the attention of investigators in the field has increasingly been drawn to the lateral preoptic region and the tissues surrounding the anterior third ventricle. The present paper reviews these developments and proposes that still another diencephalic structure, the subthalamic region known as the zona incerta, may play a major role in the regulation of thirst and water intake.

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Reversible obesity and plasma fat metabolites.

Rats were made to overeat and gain weight (about 50 g) by long-acting protamine zinc insulin (PZI) treatment. When the PZI treatment was stopped, the rats ate much less than normal for at least seven days. During recovery from PZI-induced obesity, negative correlations were observed between food intake and plasma levels of the fat metabolites, free fatty acids, glycerol, and ketone bodies. A similar but smaller effect was observed during recovery from dietary obesity (about 15 g). The plasma fat metabolites may be the blood-borne signals which suppress hunger under these conditions.

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Plasma fat metabolites and hunger.

In order to test the hypothesis that the fat metabolites are the blood-borne signals which suppress hunger during recovery from reversible obesity, experiments were designed to manipulate plasma fat metabolite levels directly. In order to elevate plasma glycerol levels, glycerol was infused intravenously into relatively unrestrained rats for 36 hours; this treatment greatly increased plasma glycerol levels but reduced voluntary food intake only slightly. Similar results were obtained when glycerol was mixed with powdered rat food. These results suggest that glycerol is not the "lipostatic hormone" although it may contribute to regulation. Similar experiments with a synthetic precursor of the ketone bodies (1,3 butanediol), suggest that the ketone bodies contribute to the decrease in food intake after reversible obesity, but cannot be a complete explanation. Dietary fat consumption raised plasma free fatty acid (FFA) levels to the range seen during recovery from reversible obesity, suggesting that plasma FFAs may be a blood-borne signal of fat utilization in both cases. Intralipid, a synthetic triglyceride emulsion designed for intravenous administration, also increased plasma FFA levels but suppressed food intake by less than predicted. However, Intralipid may tend to cause spuriously high plasma FFA readings for reasons which are discussed. These results suggest that plasma fat metabolites, especially FFAs, may be blood-borne signals which contribute to the voluntary dieting after reversible obesity.

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Early streptozotocin diabetes and hunger.

The initial effect of streptozotocin diabetes is not hyperphagia, but reduced food intake. Diabetic hyperphagia reaches maximum only after many days. Utilization of body fat may account for the delayed appearance of diabetic hyperphagia; this effect may be mediated by plasma fat metabolites. Plasma levels of free fatty acids (FFAs), ketone bodies, and glycerol are greatly elevated following STZ treatment, but return nearly to normal as diabetic hyperphagia appears.

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Iontophoretic injections of kainic acid into the rat lateral hypothalamus: effects on ingestive behavior.

Iontophoretic injections of kainic acid into the dorsolateral hypothalamus of rats resulted in localized, partial depletions of neurons from the area without significant damage to adjacent areas of the diencephalon, including the zona incerta, dorsomedial hypothalamus and anterior as well as posterior regions of the hypothalamus that have been reported to be severely affected by mechanical injections of KA into the LH. Distant KA-sensitive structures such as the hippocampus and temporal lobe also showed no discernible neuronal loss or glial proliferation. The neuronal loss within the LH was far less severe after iontophoretic injections than after mechanical injections of KA. Our KA treated animals nonetheless displayed transient aphagia and adipsia, followed by variable periods of hypophagia and hypodipsia. After recovery of essentially normal ad lib feeding, the KA-treated rats failed to eat in response to a glucoprivic challenge (2-deoxy-D-glucose) but consumed normal quantities of water during periods of food deprivation. Their drinking response to hypertonic saline was somewhat reduced during the first hour after the treatment but normal at 6 as well as 24 hours. Unilateral KA injections produced only transient changes in ad lib food intake.

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Responses to dietary adulterations in rats with zona incerta lesions.

Large lesions of the rostral zona incerta (ZI) permanently reduced food and water intake and body weight to about 75% of control levels. When quinine hydrochloride was added to the water supply, the experimental animals exhibited a somewhat greater initial decrease in fluid consumption, but otherwise responded much like control rats to quinine adulteration of both food and water. The ZI animals reduced their fluid intake when water was added to the food supply, in the form of wet mash, while the controls showed no compensation for the auxiliary water. When presented with sucrose solutions, the ZI animals increased their fluid intake, but reduced their mash consumption, to a greater degree than control rats. The experimental animals also showed an exaggerated response in both food and caloric intake to the addition of sucrose to the wet mash.

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