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N Geary

Publications and source records attributed to N Geary.

At least 19 recordsLinked to original sources
PubMed2005

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation.

The relative potencies of cholecystokinin (CCK)-8 and CCK-33 for decreasing meal size depend on the route of administration. Inhibitory potencies are equal after intraperitoneal administration, but CCK-33 is significantly more potent after intraportal administration. This suggests that CCK-33 is a more effective stimulant of hepatic afferent vagal nerves than is CCK-8. To investigate this possibility, we administered both peptides intraperitoneally in rats with abdominal vagotomies that spared only the hepatic proper vagal nerves (H) and in rats with abdominal vagotomies that spared the common hepatic branch that contains the fibers of the hepatic proper and gastroduodenal nerves (HGD). The vagal afferent innervation in H and HGD rats was verified with a wheat germ agglutinin-horseradish tracer strategy. Intraperitoneal administration of CCK-33 decreased 30-min intake of 10% sucrose in H rats as much as in sham rats, but CCK-8 decreased intake significantly less in H rats than in sham rats. The larger inhibitory effect of CCK-33 than of CCK-8 in H rats is consistent with the hypothesis that CCK-33 is a more effective stimulant of the hepatic proper vagal afferent nerves than CCK-8. In contrast to the results in H rats, the inhibitory potencies of both peptides were significantly and equivalently reduced in HGD rats compared with sham rats. This suggests that there is an inhibitory interaction between the stimulation of the gastroduodenal and hepatic proper afferent fibers by CCK-33.

Afferent Pathways↗
PubMed2005

Antipsychotic drug-induced weight gain: development of an animal model.

OBJECTIVE: Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. METHODS: Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. RESULTS: After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. CONCLUSIONS: Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

Animals↗
PubMed2001

Intrameal hepatic-portal infusion of glucose reduces spontaneous meal size in rats.

To test whether glucose (GLC) or insulin (INS) acutely reduces spontaneous meal size, we tested the effects of remotely controlled, intrameal hepatic-portal vein infusions of GLC or INS on rats' spontaneous feeding patterns. Experiment 1 included four blocks of three test infusions and one control infusion. The test infusions in each block were 0.25, 0.5, 1.0 or 1.5 mmol GLC; 2, 4, 6, or 8 mU INS; or the four combinations with dose ratios of 1 mmol GLC/8 mU INS, respectively. Control infusions and the INS vehicle were saline infusions that were equiosmotic to the GLC infusion used in that block. Infusions (0.1 ml x 5 min) were done during the first spontaneous dark-phase meal. None of the test infusions affected meal size, meal duration or the duration of the subsequent intermeal interval. In Experiment 2, a similar design was used to test infusions of 1 mmol GLC, 2 mU INS and GLC/INS. Both GLC alone and GLC/INS reduced the size and duration of the first spontaneous dark-phase meal. The subsequent intermeal interval was unaffected, but GLC alone also increased the satiety ratio (min/g) of the meal. The size and duration of the second dark-phase meal were unaffected. INS alone did not affect any meal parameters. In Experiment 3, infusions of 1 mmol GLC and 2 mU INS were repeated during each of the first three meals of the dark phase. These infusions reduced the size and duration of each meal, as well as 6-h cumulative food intake, but did not affect any other meal parameter. These experiments demonstrate for the first time that intrameal hepatic-portal infusions of GLC or of GLC and INS is sufficient to acutely and selectively reduce spontaneous meal size in the rat. The findings are consistent with the idea that meal-contingent changes in hepatic-portal GLC concentration contribute to satiation.

Animals↗
PubMed2001

Estradiol, CCK and satiation.

Estradiol has long been known to inhibit feeding in animals, but the mechanism(s) mediating its effects have not been clear. Demonstrations that estradiol's feeding effects are expressed as decreases in meal size coupled with the emerging consensus that cholecystokinin (CCK) released from the small intestines during meals is a physiological negative-feedback signal controlling meal size (i.e. satiation) suggested a new approach to the problem of the mechanisms of estradiol's inhibitory effect on feeding. Progress on this approach is reviewed here. Experimental manipulations of exogenous and endogenous CCK and estradiol have produced converging evidence that estradiol cyclically increases the activity of the CCK satiation-signaling pathway so that meal size and food intake decrease during the ovulatory or estrus phase of the ovarian cycle. This is a striking example of the modulation of the operation of a control of meal size by the physiological context in which the meal occurs. Estradiol also produces a tonic decrease in meal size, but this apparently does not involve the CCK satiation-signaling pathway. Where and how estradiol acts to increase the potency of the CCK satiating-signaling pathway are not known. Several possible sites are suggested by the observations that estradiol treatment increases feeding- and CCK-induced expression of c-Fos in ovariectomized animals in brain areas including the nucleus tractus solitarius, paraventricular nucleus of the hypothalamus, and central nucleus of the amygdala. Tests with null mutation mice indicate that estrogen receptor-alpha is necessary for estradiol's feeding effects. Finally, the possibilities that estradiol exerts important influences on normal or disordered eating in women are discussed. It is concluded that estradiol exerts a biologically significant action on CCK satiation in animals. Further research to determine whether this action of estradiol has a role in the pathogenesis, course, or treatment of disordered eating in women is indicated.

Animals↗
PubMed2001

Sex differences in disease anorexia.

Sexually differentiated responses occur in molecular, cellular, physiologic, and organismic aspects of immune-system function in relation to acquired and innate immunities. These sex differences apparently include activational effects, which depend on gonadal hormone levels in adults, and lifelong effects, which arise directly from genetic differences or organizational effects of gonadal hormones early in development that lead to lifelong sex differences. Sex differences in immune function also can have great biological significance. Despite this, the mechanisms of these effects rarely have been analyzed extensively. This is especially true of anorexia during illness or disease. Therefore, this review briefly considers 1) the biological mechanisms of sex differences; 2) sex differences in immune function; 3) clinical and experimental data related to sex differences in four diseases or disease models that involve anorexia, Crohn's inflammatory-bowel disease, cancer, turpentine inflammation, and lipopolysaccharide bacteremia; and 4) sex differences in anorexia after interleukin-1 administration.

Anorexia↗
PubMed2001

Dopamine D(2) receptors mediate amylin's acute satiety effect.

The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. Here, we investigated the influence of a pretreatment with dopamine (DA) D(1)- and D(2)-receptor antagonists on the anorectic effect of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) diet. In 24-h food-deprived rats, pretreatment with the DA D(2)-receptor antagonist raclopride [100 microg/kg (0.2 micromol/kg) ip] significantly attenuated amylin's (5 microg/kg ip) anorectic effect, whereas raclopride alone had no effect on food intake [i.e., food intakes 1 h after injection were (n = 12): NaCl/NaCl 7.3 +/- 0.5 g; NaCl/amylin 3.9 +/- 0.6; raclopride/NaCl 7.7 +/- 0.7; raclopride/amylin 5.6 +/- 0.7]. Pretreatment with another DA D(2) receptor antagonist, sulpiride [50 mg/kg (154 micromol/kg) ip], similarly reduced amylin's satiety effect, whereas pretreatment with the DA D(1)-receptor antagonist SCH-23390 [10 microg/kg (0.03 micromol/kg) ip] did not influence amylin's effect. SCH-23390, however, completely blocked the anorexia induced by D-amphetamine (0.3 mg/kg ip). These results suggest that, under the present feeding conditions, the dopaminergic system mediates part of amylin's inhibitory effect on feeding in rats when administered intraperitoneally. This seems to involve DA D(2) receptors but not D(1) receptors.

Amyloid↗
PubMed2001

Estradiol treatment increases feeding-induced c-Fos expression in the brains of ovariectomized rats.

The steroid hormone estradiol decreases meal size by increasing the potency of negative-feedback signals involved in meal termination. We used c-Fos immunohistochemistry, a marker of neuronal activation, to investigate the hypothesis that estradiol modulates the processing of feeding-induced negative-feedback signals within the nucleus of the solitary tract (NTS), the first central relay of the neuronal network controlling food intake, and within other brain regions related to the control of food intake. Chow-fed, ovariectomized rats were injected subcutaneously with 10 microg 17-beta estradiol benzoate or sesame oil vehicle on 2 consecutive days. Forty-eight hours after the second injections, 0, 5, or 10 ml of a familiar sweet milk diet were presented for 20 min at dark onset. Rats were perfused 100 min later, and brain tissue was collected and processed for c-Fos-like immunoreactivity. Feeding increased the number of c-Fos-positive cells in the NTS, the paraventricular nucleus of the hypothalamus (PVN), and the central nucleus of the amygdala (CeA) in oil-treated rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, which process negative-feedback satiation signals, but not in the rostral NTS, which processes positive-feedback gustatory signals controlling meal size. Estradiol treatment also increased feeding-induced c-Fos in the PVN and CeA. These results indicate that modest amounts of food increase neuronal activity within brain regions implicated in the control of meal size in ovariectomized rats and that estradiol treatment selectively increases this activation. They also suggest that estradiol decreases meal size by increasing feeding-related neuronal activity in multiple regions of the distributed neural network controlling meal size.

Amygdala↗
PubMed2001

Estradiol increases glucagon's satiating potency in ovariectomized rats.

Estradiol decreases meal size, food intake, and body weight in female rats. To investigate whether these effects of estradiol involve a change in the sensitivity of the signaling pathway through which pancreatic glucagon released during meals contributes to meal termination (satiation), glucagon or glucagon antibodies were infused via the hepatic portal vein in ovariectomized rats that were chronically treated with estradiol benzoate (2 microg/day sc) or vehicle alone (100 microl sesame oil). Infusions began at 1 h after dark onset, as rats were refed after 7 h of food deprivation. Glucagon (3 microg/min for 30 min) decreased feeding during the initial 45 min of food access in both groups of rats, but the inhibition was significantly greater in estradiol- than in oil-treated rats. Similarly, antagonism of endogenous glucagon by infusion of glucagon antibodies (a dose neutralizing 3 ng of glucagon in vitro during the first 3 min of refeeding) increased feeding significantly more in estradiol- than in oil-treated rats. These data indicate that an increase in the activity of the endogenous glucagon satiation-signaling pathway may be part of the mechanism for estradiol's inhibitory effect on feeding.

Animals↗
PubMed2001

Physiological effect of circulating glucagon on the hepatic membrane potential.

The pancreatic hormone glucagon hyperpolarizes the liver cell membrane under various conditions. Here we investigated the physiological relevance of this effect by testing the influence of infusions of glucagon antiserum on the liver cell membrane potential in vivo. Intracellular microelectrode recordings of liver cells (up to 60/rat over 2 h) were done in anesthetized male rats. Livers were fixed in place, and recordings were done 10-30 min after intraperitoneal injections of glucagon or hepatic portal vein infusions of glucagon or specific polyclonal glucagon antibodies raised in rabbits. The isotonic lactose vehicle was used as a control for glucagon, and equal amounts of nonimmunized rabbit IgG were used as a control for glucagon antibodies. Intraperitoneal glucagon (400 microg/kg) hyperpolarized the liver cell membrane up to 12 mV, and intraportal glucagon (10 or 60 microg/kg) dose dependently hyperpolarized the liver cell membrane by 3-7 mV. Intraportal infusion of glucagon antiserum (in vitro binding capacity of 4 ng glucagon/rat) significantly depolarized the liver cell membrane by approximately 2.5 mV. The effects of both glucagon and glucagon antiserum reversed after 60-90 min. We conclude that glucagon is a physiologically important modulator of the liver cell membrane potential.

Animals↗
PubMed2001

Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice.

To test the role of gene expression of the classical ER (ER alpha) in the inhibitory effects of E on food intake and body weight, we ovariectomized and administered E2 benzoate (75 pg/d) or vehicle to wild-type (WT) mice and mice with a null mutation of ER alpha (alpha ERKO). Mice were ovariectomized at age 9 wk, at which time there was no significant effect of genotype on food intake or body weight. During an 18-d test after recovery from ovariectomy, vehicle-treated WT mice increased daily food intake and gained more body weight than E2-treated WT mice, whereas food intake and body weight gain were not different in E2- and vehicle-treated alpha ERKO mice. Carcass analysis revealed parallel changes in body lipid content, but not water or protein content. Because an increase in the potency of the peripheral cholecystokinin (CCK) satiation-signaling system mediates part of E2's influence on feeding in rats, the influence of ip injections of 250 microg of the selective CCK(A) receptor antagonist devazepide was then tested. Devazepide increased 3-h food intake in E2-treated WT mice, but was ineffective in both groups of alpha ERKO mice. Furthermore, ip injections of 4 microg/kg CCK-8 increased the number of cells expressing c-Fos immunoreactivity in the nuclei of the solitary tract of E2-treated WT mice more than it did in vehicle-treated WT mice, whereas E2 had no such effect in alpha ERKO mice. Thus, ER alpha is necessary for normal responsivity of food intake, body weight, adiposity, and the peripheral CCK satiation-signaling system to E2 in mice, and ER beta is not sufficient for any of these effects. This is the first demonstration that ER alpha gene expression is involved in the estrogenic control of feeding behavior and weight regulation of female mice.

Animals↗
PubMed1999

Cyclic estradiol treatment normalizes body weight and test meal size in ovariectomized rats.

We tested whether cyclic estradiol treatment, like continuous estradiol treatment, is sufficient to normalize meal size and body weight in ovariectomized rats. In Experiment 1, adult Long-Evans rats were ovariectomized and subcutaneously injected with 0, 0.2, or 2.0 microg estradiol benzoate (EB) in sesame oil each Tuesday and Wednesday. Oil-treated ovariectomized rats gained more weight during 4 weeks of ad lib feeding (48 +/- 5 g) than intact rats (16 +/- 1 g, p < 0.01). Cyclic treatment with 2.0 microg EB normalized weight gain (11 +/- 2 g). During the next week, plasma samples were assayed for estradiol. Cyclic treatment with 2.0 microg EB produced excursions of plasma estradiol that appeared similar to those of intact, cycling rats: estradiol level reached 190 +/- 60 pmol/L after the second EB injection before decreasing to undetectable levels (<30 pmol/L) by cycle end. In Experiment 2, test meal sizes after overnight food deprivation were measured. Cyclic treatment with 2.0 microg EB produced both tonic (i.e., at cycle onset, meal size was smaller in estradiol-treated than oil-treated rats) and phasic (i.e., meal size was smaller late in the EB-treatment cycle than early in it) decreases in meal size. Thus, a weekly cyclic regimen of estradiol treatment that produces changes in plasma estradiol concentration similar to those in intact cycling rats is sufficient to produce the body weight and meal size patterns that characterize normal hypothalamic-pituitary-gonadal function.

Animals↗
PubMed1999

Cyclic estradiol treatment phasically potentiates endogenous cholecystokinin's satiating action in ovariectomized rats.

The influence of ovarian cycling and of exogenous estradiol on the cholecystokinin (CCK) satiety-signalling system was investigated in intact and ovariectomized Long-Evans rats, respectively. Intraperitoneal injection of 1 mg/kg devazepide, the most potent and selective CCK(A) receptor antagonist, increased test meal size during estrus, but not during diestrus, confirming the influence of hypothalamic-pituitary-gonadal function on CCK satiety in intact rats. Devazepide was then tested in ovariectomized rats that received chronic cyclic estradiol (2 microg estradiol benzoate on Tuesday and Wednesday each week) or oil treatment. Devazepide did not increase meal size in estradiol-treated rats on Tuesday, prior to estradiol treatment, compared to oil-treated rats, but did selectively increase meal size on Friday, late in the estradiol replacement cycle, compared to Tuesday, early in the cycle. These results suggest that a phasic potentiation of the endogenous CCK satiety-signalling system is part of the mechanism for the decrease in meal size in female rats during estrus.

Animals↗
PubMed1999

Endogenous cholecystokinin's satiating action increases during estrus in female rats.

Food intake and meal size are reduced in female Long-Evans rats during estrus. To investigate the contribution of the satiating action of endogenous cholecystokinin (CCK) to this, rats were injected with 1 mg/kg of the potent, selective CCK(A) receptor antagonist, devazepide, during diestrus, when meal size is maximal, and during estrus, when it is minimal. Devazepide increased spontaneous food intake and meal size during estrus, but not during diestrus. Meal frequency was not affected by devazepide treatment. These results indicate that the potency of the CCK satiety-signaling system increases during estrus.

Animals↗
PubMed1999

Prior pregastric food stimulation and gastrin-releasing peptide1-27 (GRP) synergize to inhibit sham feeding.

The hypothesis that prior pregastric food stimulation is sufficient to reveal an inhibitory effect of gastrin-releasing peptide1-27 (GRP) on sham feeding was tested in 11 male rats equipped with chronic gastric cannulas. Rats were sham fed a high-carbohydrate solution during a 45-min test session, after 17-h food deprivation. GRP (16 or 32 microg/kg) or saline was injected intraperitoneally either at the onset or 5 or 15 min after the onset of sham feeding. This allowed for a 0-, 5-, or 15-min period of pregastric food stimulation before GRP or saline injections. Sham intake was recorded every 5 min, and behavior was observed every minute. GRP inhibited sham feeding when it was administered after 5 or 15 min of prior pregastric food stimulation, but not when it was administered at test onset. A nonsignificant increase in resting behavior and decrease in feeding behavior were associated with the decrease in sham feeding. No anomalous behaviors were noted. We conclude that a synergy between GRP and prior pregastric, presumably oral, food stimulation is sufficient to inhibit sham feeding.

Animals↗
PubMed1999

Effects of glucagon, insulin, amylin and CGRP on feeding.

The roles of the pancreatic peptides glucagon, insulin, and amylin in the inhibitory control of feeding are reviewed. Calcitonin gene-related peptide (CGRP) is also included because it is structurally and functionally related to amylin and because known amylin and CRRP receptors are activated by both peptides. Glucagon-like peptide 1, in contrast, is structurally distinct from pancreatic glucagon and does not cross-react with glucagon receptors, so it is not considered. Several detailed reviews of the feeding effects of these peptides have appeared recently; where appropriate, these are cited rather than the primary literature.

Amyloid↗
PubMed1998

Intracerebroventricular glucagon-like peptide-1 (7-36) amide inhibits sham feeding in rats without eliciting satiety.

Glucagonlike peptide-1 (7-36) amide (GLP-1) and its receptors are present in several brain regions and may play a role in the physiological control of feeding. To investigate the effect of GLP-1 on eating in the absence of postingestive food stimuli, rats were implanted with gastric cannulas for sham feeding and lateral ventricular cannulas for infusion of GLP-1. Rats (n = 10) sham fed 0.8 mol/L sucrose for 45 min, beginning 5 min after intracerebroventricular (icv) infusion of 2.5 microL of artificial cerebrospinal fluid with 0-30 microg of GLP-1 . Behaviors were observed each minute using a time-sampling technique. Additionally, lick-by-lick records of the microstructural pattern of sucrose intake were made during the first 15 min of each test for five rats receiving 3 and 10 microg of GLP-1. GLP-1 decreased sham-fed intake by as much as 50%, but GLP-1 did not terminate sham feeding. The frequency of observations of feeding was decreased, but the frequency of resting, the terminal item in the behavioral sequence of postprandial satiety in real feeding rats, did not reliably increase. No abnormal behaviors were observed. Although GLP-I did not affect the latency to begin sham feeding, it significantly reduced the initial rate of licking. GLP-I did not affect the motor aspects of licking, because the interlick intervals within individual bursts of licking or overall lick efficiency were normal. These data suggest that intracerebroventricular infusions of GLP-1 inhibit sham feeding by decreasing the orosensory positive feedback that drives licking, rather than by activating physiological satiating mechanisms or nonspecific mechanisms such as aversion or motor incapacity.

Animals↗
PubMed1998

Behaviorally specific inhibition of sham feeding by amylin.

To further characterize amylin's inhibitory action on feeding, we examined the effects of intraperitoneal injections of amylin on sham feeding of sucrose in food-deprived male rats with chronic gastric cannulas. Thirty and 100 microg/kg amylin reduced sham feeding, but did not terminate it or elicit the behavioral sequence of satiety. Real feeding of sucrose, but not sham feeding, was reduced after injection of 10 microg/kg amylin. Amylin's inhibitory effect on sham feeding appeared behaviorally specific because neither 30 nor 100 microg/kg amylin affected sham drinking of water in thirsty rats and because no abnormal behaviors occurred. We conclude that amylin has a behaviorally specific satiating effect on sucrose sham feeding that is insufficient to elicit satiety in absence of gastric or postgastric food stimulation.

Amyloid↗