Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats

2001 ◽  
Vol 281 (6) ◽  
pp. R1907-R1916 ◽  
Author(s):  
Tomoi Sato ◽  
Michael M. Meguid ◽  
Sergueï O. Fetissov ◽  
Chung Chen ◽  
Lihua Zhang
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Meal Size ◽  
Feeding Pattern ◽  
Hypothalamic Nucleus ◽  
Receptor Subtypes ◽  
Dopaminergic Receptor ◽  
Receptor Mrna ◽  
Tumor Bearing ◽  
Free Feeding

Our past microdialysis studies in ventromedial hypothalamic nucleus (VMN) and lateral hypothalamic area (LHA) of changes in dopamine concentrations in response to changes in food intake [characterized as feeding pattern (changes in meal number and size)] in anorexia of cancer show abnormal presynaptic dopaminergic neurotransmission. To determine postsynaptic receptor status, studies were done in tumor-bearing (TB) and non-tumor-bearing (NTB) free-feeding control rats while continuously measuring their food intake via a rat eater meter. When TB rats developed anorexia, TB and control rats were killed, and postsynaptic D1- and D2-receptor mRNA expression in LHA and VMN were measured via RT-PCR. At anorexia, food intake decreased initially by a decrease in meal number, whereas a concurrent increase in meal size occurred for 24 h in an attempt to maintain food intake constant. Then meal size also decreased. At this time, D1- and D2-receptor mRNA expressions in LHA and VMN of TB vs. controls were significantly upregulated. Verification of D1- or D2-receptor changes to changes in meal number and size at anorexia was made by injection of intra-VMN or -LHA dopaminergic receptor antagonists. Intra-VMN D1-receptor antagonist (SCH-23390) in TB rats decreased food intake mainly via a decrease in meal size. Intra-VMN D2-receptor antagonist (sulpiride) in TB rats increased food intake via an increase in meal number and in NTB free-feeding rats by an increase in meal size. Intra-LHA D1-receptor antagonist in TB rats had no effect on food intake or feeding pattern. Intra-LHA D2-receptor antagonist in TB and in NTB free-feeding rats increased food intake via an increase in meal number. Our data provide evidence that postsynaptic dopaminergic receptor subtypes in the hypothalamus are involved in the regulation of meal size, meal number, and thus food intake in anorectic TB rats.

scholarly journals Reduced Ghrelin Secretion in the Hypothalamus of Rats due to Cisplatin-Induced Anorexia

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3773-3782 ◽  
Author(s):  
Koji Yakabi ◽  
Chiharu Sadakane ◽  
Masamichi Noguchi ◽  
Shino Ohno ◽  
Shoki Ro ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
Serotonin 2C Receptor ◽  
Receptor Mrna ◽  
Gastrointestinal Side Effects ◽  
Ghrelin Secretion ◽  
Fasted Rats

Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients’ quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats

1999 ◽  
Vol 277 (3) ◽  
pp. R850-R855 ◽  
Author(s):  
Giovanni F. Torelli ◽  
Michael M. Meguid ◽  
Lyle L. Moldawer ◽  
Carl K. Edwards ◽  
Hyune-Ju Kim ◽  
...  
Keyword(s):  
Food Intake ◽  
Tumor Growth ◽  
Meal Size ◽  
Male Rats ◽  
Type I ◽  
Tnf Inhibitor ◽  
Tnf Receptor ◽  
Tumor Bearing ◽  
Tnf Α ◽  
Soluble Tnf Receptor

With progression of tumor growth, rats demonstrate anorexia and reduced food intake, a function of meal number and meal size. Tumor necrosis factor-α (TNF-α), a recognized anorectic agent, reacts with two different receptors (type I: 55 kDa; type II: 75 kDa). We used a dimeric, pegylated 55-kDa TNF receptor construct to test its effects on food intake, meal number, and meal size, which were continuously measured with a rat eater meter in 16 Fischer 344 male rats injected with 106 viable methylcholanthrene cells. When anorexia developed, rats received a subcutaneous injection of either 0.25 mg/kg body wt of soluble TNF receptor construct (study) or vehicle (tumor-bearing control). Before TNF inhibitor injection, no differences were observed in food intake, meal number, or meal size between the two groups. After the TNF inhibitor injection, study vs. control rats significantly improved food intake as a result of an increase in meal number and meal size. Rats also showed a significant improvement in body weight. These data suggest that TNF-α, in addition to other cytokines, contributes to the anorexia of tumor growth, probably mediated via the hypothalamus.

Cholecystokinin octapeptide decreases food intake in white-crowned sparrows

1993 ◽  
Vol 264 (5) ◽  
pp. R852-R856
Author(s):  
R. D. Richardson ◽  
T. Boswell ◽  
S. C. Weatherford ◽  
J. C. Wingfield ◽  
S. C. Woods
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Mammalian Species ◽  
Meal Size ◽  
Dark Cycle ◽  
Cholecystokinin Octapeptide ◽  
Dose Dependent Fashion ◽  
Cck Receptor Antagonist ◽  
Dose Dependent ◽  
Short Days

White-crowned sparrows maintained on short days (9:15-h light-dark cycle) were peripherally injected with 1.0, 4.0, and 16 micrograms/kg ip of cholecystokinin octapeptide (CCK-8). Meal size over the subsequent 30 min was significantly depressed in a dose-dependent fashion. Water intake was not affected. The anorexic effect caused by 4.0 micrograms/kg was attenuated by 100 micrograms/kg of the type-A CCK receptor antagonist MK-329 but not by 300 micrograms/kg of the type-B CCK receptor antagonist L 365,260, suggesting that CCK-induced suppression of food intake in this species is mediated by a CCK-A receptor. Administration of both CCK-A and CCK-B receptor antagonists alone resulted in no change in meal size. These experiments suggest that white-crowned sparrows, when weight stable, respond to CCK-8 in a manner comparable with several mammalian species.

scholarly journals Systemic Nicotine Administration Suppresses Food Intake Via Reduced Meal Sizes in Both Male and Female Rats

1998 ◽  
Vol 41 (4) ◽  
pp. 167-173 ◽  
Author(s):  
Vladimír Bláha ◽  
Zhong-jin Yang ◽  
Michael Meguid ◽  
Jia-ke Chai ◽  
Zdeněk Zadák
Keyword(s):  
Food Intake ◽  
Suppressive Effect ◽  
Meal Size ◽  
Female Rats ◽  
Feeding Pattern ◽  
Male And Female ◽  
Fischer 344 ◽  
Nicotine Administration ◽  
Male And Female Rats ◽  
Cyclical Pattern

The appetite suppressing effect of tobacco products, via the main pharmacological agent nicotine, is a major reason for its usage both by woman and man. Food intake (FI) could be changed by altering either meal size (MZ) or meal number (MN), which are regulated dependently in a reciprocal manner. The present study investigated the effect of systemic nicotine administration on the rat feeding pattern. Because of gender differences in the effects of nicotine, both male and female rats were studied. Alzet mini-osmotic pumps (Model 2001) and the automated rat eatometer were used to evaluate the feeding pattern of male and female Fischer 344 rats during seven days of systemic nicotine infusion (6 mg/kg b.w. s.c.). The main findings are: 1) systemic nicotine infusion decreased food intake in both sexes; 2) the decreased food intake was due to significantly reduced meal sizes while meal numbers were not altered significantly in either males or females; 3) the cyclical pattern of vaginal smears, food intake, meal number and meal size of female rats was not affected by nicotine administration. We conclude that the feeding suppressive effect of nicotine, which is due to reduced meal sizes and thus satiation, is not sex-hormones related.

Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats

1984 ◽  
Vol 246 (5) ◽  
pp. R776-R787 ◽  
Author(s):  
D. B. West ◽  
D. Fey ◽  
S. C. Woods
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Physiological Saline ◽  
Meal Size ◽  
Base Line ◽  
Drinking Patterns ◽  
Daily Food ◽  
Food And Water Intake ◽  
Dramatic Shift ◽  
Free Feeding

Food and water intake of free-feeding rats with indwelling intraperitoneal catheters connected to infusion pumps was continuously monitored and recorded by a microcomputer-based data acquisition system. Initially, at the start of every spontaneous meal for 4 days, each rat was infused with 0.27 ml of physiological saline. Saline infusion did not affect any feeding or drinking patterns, and the rate of weight gain remained unchanged. For 6 subsequent days, the octapeptide of cholecystokinin (CCK-8, 1.1 micrograms/meal) dissolved in physiological saline was infused at the onset of each meal. CCK-8 infusion caused a dramatic shift of patterns of food intake. Average meal size was reduced by at least 44%, whereas daily meal number increased by 162% or more for all 6 days of CCK-8 infusion. Total daily food intake recovered to predrug levels by the 4th day of CCK-8 infusion, primarily due to increased feeding frequency. Average body weight dropped by 12.4 g on the 1st day of CCK infusion, but over the following 5 days the growth rate was not different from the base-line predrug rate. With discontinuation of CCK-8 infusion all meal patterns returned rapidly to normal and body weight immediately recovered.

Intracerebroventricular administration of MK-801 increases food intake through mechanisms independent of gastric emptying

2004 ◽  
Vol 287 (6) ◽  
pp. R1462-R1467 ◽  
Author(s):  
M. Covasa ◽  
Chun-Yi Hung ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Meal Size ◽  
Sucrose Intake ◽  
Intracerebroventricular Administration ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Parallel Experiment

Systemic or hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate receptor antagonist, increases meal size. To examine whether MK-801 enhances intake by increasing gastric emptying, we administered MK-801 (2.0 μg/3.0 μl) into the fourth ventricle [intracerebroventricular (ICV)] and measured feeding and gastric emptying of 5-ml NaCl or 15% sucrose loads. In a parallel experiment, we examined food intake and gastric emptying following intraperitoneal (IP) injection of MK-801 (100 μg/kg). MK-801, either IP or ICV, increased 30-min sucrose intake compared with control (12.3 ± 0.7 vs. 9.8 ± 0.5 and 16.6 ± 2.0 vs. 10.7 ± 0.7 ml, for IP and ICV administration, respectively). Also, IP MK-801 increased 5-min gastric emptying of NaCl (4.13 ± 0.1 ml emptied) and sucrose (3.11 ± 0.1 ml emptied) compared with control (3.75 ± 0.2 and 2.28 ± 0.1 ml emptied for NaCl and sucrose loads, respectively). In contrast, ICV MK-801 did not alter NaCl emptying (3.82 ± 0.1 ml emptied) compared with control (3.82 ± 0.3 ml emptied) and actually reduced gastric emptying of sucrose (2.1 ± 0.2 and 2.94 ± 0.1 ml emptied, for MK and vehicle, respectively). These data confirm previous results that systemic as well as hindbrain injection of MK-801 increases food intake. However, because ICV MK-801 failed to increase gastric emptying, these results indicate that MK-801 increases food intake through mechanisms independent of altered gastric emptying.

Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake

2007 ◽  
Vol 293 (4) ◽  
pp. R1490-R1494 ◽  
Author(s):  
Chun Min Lo ◽  
Dian Ming Zhang ◽  
Kevin Pearson ◽  
Liyun Ma ◽  
William Sun ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Intraperitoneal Administration ◽  
Significant Inhibition ◽  
Meal Size ◽  
Saline Control ◽  
Reduce Food Intake ◽  
Satiation Effect ◽  
Threshold Levels ◽  
Cck1 Receptor

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 μg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 μg/kg. Doses of apo AIV (50 μg/kg) or CCK (0.06 μg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls ( P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.

The microinjection of AMPA receptor antagonist into the accumbens shell failed to change food intake, but reduced fear-motivated behaviour in free-feeding female rats

2008 ◽  
Vol 193 (2) ◽  
pp. 243-247 ◽  
Author(s):  
Isabel Cristina da Cunha ◽  
Aparecida Marcelino de Nazareth ◽  
Juliano Cordova Vargas ◽  
Adriana Ferraz ◽  
José Marino Neto ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Female Rats ◽  
Ampa Receptor Antagonist ◽  
Free Feeding

scholarly journals Evidence That the Inhibition of Luteinizing Hormone Secretion Exerted by Central Administration of Neuropeptide Y (NPY) in the Rat Is Predominantly Mediated by the NPY-Y5 Receptor Subtype1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4046-4055 ◽  
Author(s):  
Paula D. Raposinho ◽  
Pierre Broqua ◽  
Dominique D. Pierroz ◽  
Amanda Hayward ◽  
Yvan Dumont ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Pancreatic Polypeptide ◽  
Inhibitory Action ◽  
Receptor Subtypes ◽  
Y1 Receptor ◽  
Npy Receptor ◽  
Gonadotropic Axis ◽  
Lh Secretion

Abstract A number of studies have indicated that neuropeptide Y (NPY) is a central regulator of the gonadotropic axis, and the Y1 receptor was initially suggested to be implicated. As at least five different NPY receptor subtypes have now been characterized, the aim of the present study was to reinvestigate the pharmacological profile of the receptor(s) mediating the inhibitory action of NPY on LH secretion by using a panel of NPY analogs with different selectivity toward the five NPY receptor subtypes. When given intracerebroventricularly (icv) to castrated rats, a bolus injection of native NPY (0.7–2.3 nmol) dose-dependently decreased plasma LH. Peptide YY (PYY; 2.3 nmol) was as potent as NPY, suggesting that the Y3 receptor is not implicated. Confirming previous data, the mixed Y1, Y4, and Y5 agonist[ Leu31,Pro34]NPY (0.7–2.3 nmol) inhibited LH release with potency and efficacy equal to those of NPY. Neither the selective Y2 agonist C2-NPY (2.3 nmol) nor the selective Y4 agonist rat pancreatic polypeptide affected plasma LH, excluding Y2 and Y4 subtypes for the action of NPY on LH secretion. The mixed Y4-Y5 agonist human pancreatic polypeptide (0.7–7 nmol) as well as the mixed Y2-Y5 agonist PYY3–36 (0.7–7 nmol) that displayed very low affinity for the Y1 receptor, thus practically representing selective Y5 agonists in this system, decreased plasma LH with potency and efficacy similar to those of NPY, indicating that the Y5 receptor is mainly involved in this inhibitory action of NPY on LH secretion.[ d-Trp32]NPY, a selective, but weak, Y5 agonist, also inhibited plasma LH at a dose of 7 nmol. Furthermore, the inhibitory action of NPY (0.7 nmol) on LH secretion could be fully prevented, in a dose-dependent manner (6–100 μg, icv), by a nonpeptidic Y5 receptor antagonist. This antagonist (60 μg, icv) also inhibited the stimulatory action of NPY (0.7 nmol) on food intake. The selectivity of PYY3–36, human PP,[ d-Trp32]NPY, and the Y5 antagonist for the Y5 receptor subtype was further confirmed by their ability to inhibit the specific[ 125I][Leu31,Pro34]PYY binding to rat brain membrane homogenates in the presence of the Y1 receptor antagonist BIBP3226, a binding assay system that was described as being highly specific for Y5-like receptors. With the exception of[ d-Trp32]NPY, all analogs able to inhibit LH secretion were also able to stimulate food intake. Taken together, these results indicate that the Y5 receptor is involved in the negative control by NPY of the gonadotropic axis.

scholarly journals Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Dark Phase ◽  
Light Phase ◽  
Dark Cycle ◽  
Simultaneous Activation ◽  
Type 3 ◽  
G Protein Coupled

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

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