NMDA receptor participation in control of food intake by the stomach

2000 ◽  
Vol 278 (5) ◽  
pp. R1362-R1368 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter ◽  
Gilbert A. Burns
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Nmda Receptors ◽  
Nmda Antagonist ◽  
Meal Size ◽  
Sham Feeding ◽  
Gastric Emptying Rate ◽  
Mk 801 ◽  
Direct Measurements ◽  
Increase Food Intake

We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl-d-aspartate (NMDA)-type glutamate receptors, increased meal size and duration in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggested that the MK-801-induced increase in meal size did not depend on antagonism of postgastric satiety signals. Consequently, we hypothesized that the NMDA antagonist might increase food intake by directly antagonizing gastric mechanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded intake of 15% sucrose in rats implanted with pyloric cuffs that could be closed to prevent gastric emptying. Sucrose intake was increased when the pyloric cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention of all ingested sucrose. Direct measurements of gastric emptying revealed that MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucrose. Furthermore, MK-801 also accelerated the rate of emptying of freely ingested sucrose regardless of the volume ingested. Taken together with our previous findings, these results indicate that blockade of NMDA receptors with MK-801 does not increase food intake by antagonizing gastric mechanosensation. Rather, it accelerates gastric emptying, and thereby may indirectly reduce gastric mechanoreceptive cues, resulting in prolongation of eating. Modulation of gastric emptying rate by NMDA receptors could play an important role in the control of meal sizes.

NMDA receptor blockade attenuates CCK-induced reduction of real feeding but not sham feeding

2004 ◽  
Vol 286 (5) ◽  
pp. R826-R831 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter ◽  
Gilbert A. Burns
Keyword(s):  
Gastric Emptying ◽  
Ion Channels ◽  
Nmda Receptor ◽  
Food Intake ◽  
Receptor Blockade ◽  
Sham Feeding ◽  
Systemic Injection ◽  
Mk 801 ◽  
Nmda Receptor Blockade ◽  
Series Of Experiments

Systemic injection of MK-801, a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptor ion channels, increases meal size and delays satiation. We examined whether MK-801 increases food intake by directly interfering with actions of cholecystokinin (CCK). Prior administration of MK-801 (100 μg/kg ip) reversed the inhibitory effects of CCK-8 (2 and 4 μg/kg ip) on real feeding of both liquid and solid foods. MK-801 alone did not alter 30-min sham intake of 15% sucrose compared with intake after saline. Furthermore, while CCK-8 (2 or 4 μg/kg ip) reduced sham intake, this reduction was not attenuated by MK-801 pretreatment. To ascertain whether MK-801 attenuation of CCK-induced reduction of real feeding was associated with attenuated inhibition of gastric emptying, we tested the effect of MK-801 pretreatment on CCK-induced inhibition of gastric emptying of 5-ml saline loads. Ten-minute gastric emptying was accelerated after MK-801 (3.9 ± 0.2 ml) compared with saline vehicle (2.72 ± 0.2 ml). CCK-8 (0.5 μg/kg ip) reduced 10-min emptying to 1.36 ± 0.3 ml. Pretreatment with MK-801 did not significantly attenuate CCK-8-induced reduction of gastric emptying (0.9 ± 0.4 ml). This series of experiments demonstrates that blockade of NMDA ion channels reverses inhibition of real feeding by CCK. However, neither inhibition of sham feeding nor inhibition of gastric emptying by CCK is attenuated by MK-801. Therefore, increased food intake after NMDA receptor blockade is not caused by a direct interference with CCK-induced satiation. Rather, increased real feeding, either in the presence or absence of CCK, depends on blockade of NMDA receptor participation in other postoral feedback signals such as gastric sensation or gastric tone.

NMDA channels control meal size via central vagal afferent terminals

2005 ◽  
Vol 289 (5) ◽  
pp. R1504-R1511 ◽  
Author(s):  
B. R. Gillespie ◽  
G. A. Burns ◽  
R. C. Ritter
Keyword(s):  
Food Intake ◽  
Ion Channel ◽  
Nmda Receptors ◽  
Higher Order ◽  
Meal Size ◽  
Vagal Afferents ◽  
Sucrose Intake ◽  
Mk 801 ◽  
Vagal Afferent ◽  
Afferent Terminals

The N-methyl-d-aspartate (NMDA) ion channel blocker MK-801 administered systemically or as a nanoliter injection into the nucleus of the solitary tract (NTS), increases meal size. Furthermore, we have observed that ablation of the NTS abolishes increased meal size following systemic injection of dizocilpine (MK-801) and that MK-801-induced increases in intake are attenuated in rats pretreated with capsaicin to destroy small, unmyelinated, primary afferent neurons. These findings led us to hypothesize that NMDA receptors on central vagal afferent terminals or on higher-order NTS neurons innervated by these vagal afferents might mediate increased food intake. To evaluate this hypothesis, we examined 15% sucrose intake after 50-nl MK-801 injections ipsilateral or contralateral to unilateral nodose ganglion removal (ganglionectomy). On the side contralateral to ganglionectomy, vagal afferent terminals would be intact and functional, whereas ipsilateral to ganglionectomy vagal afferent terminals would be absent. Three additional control preparations also were included: 1) sham ganglionectomy and 2) subnodose vagotomy either contralateral or ipsilateral to NTS cannula placement. We found that rats with subnodose vagotomies increased their sucrose intake after injections of MK-801 compared with saline, regardless of whether injections were made contralateral (12.6 ± 0.2 vs. 9.6 ± 0.3 ml) or ipsilateral (14.2 ± 0.6 vs. 9.7 ± 0.4 ml) to vagotomy. Rats with NTS cannula placements contralateral to nodose ganglionectomy also increased their intake after MK-801 (12.2 ± 0.9 and 9.2 ± 1.1 ml for MK-801 and saline, respectively). However, rats with placements ipsilateral to ganglionectomy did not respond to MK-801 (8.0 ± 0.5 ml) compared with saline (8.3 ± 0.4 ml). We conclude that central vagal afferent terminals are necessary for increased food intake in response to NMDA ion channel blockade. The function of central vagal afferent processes or the activity of higher-order NTS neurons driven by vagal afferents may be modulated by NMDA receptors to control meal size.

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.

scholarly journals Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat

2006 ◽  
Vol 290 (3) ◽  
pp. R642-R651 ◽  
Author(s):  
Chun-Yi Hung ◽  
M. Covasa ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Nmda Receptor Antagonist ◽  
Saline Control ◽  
Sucrose Intake ◽  
Mk 801

Hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or d(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 ± 0.4 ml, saline control) (11.0 ± 0.8, 11.2 ± 1.0, 11.2 ± 1.0, 13.1 ± 2.2, and 11.0 ± 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 μg (16.7 ± 0.6 ml) and 0.4 μg (14.9 ± 0.5 ml) but not 0.1 and 0.6 μg of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 ± 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 ± 0.1 g vs. saline: 27.1 ± 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 ± 0.7ml, vs. saline: 10.5 ± 0.5ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 ± 0.7 ml vs. saline: 14.6 ± 1.7 ml), and 60-min (AP5: 19.4 ± 0.6 ml vs. saline: 15.5 ± 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 ± 0.3 g vs. saline: 26.1 ± 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

Analyses of Gastric Emptying in Bluegill (Lepomis macrochirus)

1976 ◽  
Vol 33 (7) ◽  
pp. 1630-1633 ◽  
Author(s):  
F. M. El-Shamy
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Multiple Regression ◽  
Statistical Models ◽  
Lepomis Macrochirus ◽  
Meal Size ◽  
Equivalent Amount ◽  
Single Meal ◽  
Time Of Feeding

Bluegill (Lepomis macrochirus) fed a single meal averaging 111.6 mg dry wt (2.19% body wt on a wet fish and food basis) showed an average of 60 mg (54%) of the meal remaining after 8 h of digestion compared to 71 mg (59%) of an equivalent amount of food (119.6 mg or 2.04% body wt) fed in two consecutive meals. Fish fed a single meal averaging 167.2 mg (2.74% body wt) showed an average of 41% of the meal remaining 12 h after feeding, while fish fed three consecutive meals totaling 140.3 mg (2.51% body wt), showed an average of 47% of the food intake remaining 12 h after they were first fed. Two statistical models — an exponential and a multiple regression — relating food digested to meal size and time of feeding were developed. Both statistical models, when based on results of fish fed single meals, failed to predict values comparable to those observed for bluegill fed multiple meals.

scholarly journals Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers

2007 ◽  
pp. 315-322 ◽  
Author(s):  
B Çakır ◽  
Ö Kasımay ◽  
E Devseren ◽  
BÇ Yeğen
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Receptor Blocker ◽  
Adrenergic Blockade ◽  
Phenol Red ◽  
Gastric Emptying Rate ◽  
Cck Receptors ◽  
Afferent Fibers ◽  
Cephalic Phase ◽  
Vagal Afferent

Leptin regulates energy homeostasis and body weight by balancing energy intake and expenditure. It was recently reported that leptin, released into the gut lumen during the cephalic phase of gastric secretion, is capable of initiating intestinal nutrient absorption. Vagal afferent neurons also express receptors for both CCK and leptin, which are believed to interact in controlling food intake. The present study was undertaken to investigate the central and peripheral effects of leptin on gastric emptying rate. Under anesthesia, male Sprague-Dawley rats (250-300 g) were fitted with gastric Gregory cannulas (n=12) and some had additional cerebroventricular cannulas inserted into their right lateral ventricles. Following recovery, the rate of gastric emptying of saline (300 mOsm/kg H(2)O) was determined after instillation into the gastric fistula (3 ml, 37 degrees C, containing phenol red, 60 mg/l as a non-absorbable dilution marker). Gastric emptying rate was determined from the volume and phenol red concentrations recovered after 5 min. Leptin, injected intraperitoneally (i.p.; 10, 30, 60, 100 microg/kg) or intracerebroventricularly (i.c.v.; 5, 15 microg/rat) 15 min before the emptying, delayed gastric emptying rate of saline at the dose of 30 microg/kg or 15 microg/rat (p<0.001). When CCK(1) receptor blocker L-364,718 (1 mg/kg, i.p.), CCK(2) receptor blocker L-365,260 (1 mg/kg, ip) or adrenergic ganglion blocker bretylium tosylate (15 mg/kg, i.p.) was administered 15 min before ip leptin (30 microg/kg) injections, leptin-induced delay in gastric emptying was abolished only by the CCK(1) receptor blocker (p<0.001). However, the inhibitory effect of central leptin on gastric emptying was reversed by adrenergic blockade, but not by either CCK antagonists. Our results demonstrated that leptin delays gastric emptying. The peripheral effect of leptin on gastric motility appears to be mediated by CCK(1) receptors, suggesting the release of CCK and the involvement of vagal afferent fibers. On the other hand, the central effect of leptin on gastric emptying is likely to be mediated by adrenergic neurons. These results indicate the existence of a functional interaction between leptin and CCK receptors leading to inhibition of gastric emptying and short-term suppression of food intake, providing an additional feedback control in producing satiety.

scholarly journals Postgraduate Symposium The role of fat in gastric emptying and satiety: acute and chronic effects

2009 ◽  
Vol 68 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Miriam Clegg ◽  
Amir Shafat
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Gastrointestinal Transit ◽  
Positive Energy ◽  
Low Fat ◽  
Low Fat Diet ◽  
The Metabolic Syndrome ◽  
Increase Food Intake ◽  
Positive Energy Balance

Dietary fat is an important factor in the aetiology of obesity and the metabolic syndrome. It has been widely debated whether gastric emptying (GE) is altered in obesity. GE times have been reported as both longer and shorter in obese individuals compared with matched lean individuals. However, the general consensus is that GE is accelerated and satiety is lower in obesity. Research has implicated a high-fat (HF) diet in these findings. A single HF meal has a longer GE time than a low-fat meal and can even delay GE of the subsequent meal. However, an HF diet has shown different effects. Feeding a HF diet adapts gastrointestinal function to reduce GE times in comparison with a low-fat diet. Increased GE may lead to decreased satiety and faster onset of subsequent eating episodes. Further results have suggested that consuming an HF diet for 14 d increases the GE rate of HF food but not low-fat food. Consuming HF diets for 2 weeks has also been shown to increase food intake. Decreased satiation following an HF diet may cause increased food intake and a positive energy balance, potentially resulting in a gradual increase in adiposity. Recent results have suggested that gastrointestinal transit is accelerated following only 3 d on a HF diet. The variable GE times reported in obesity may be associated with interactions between the HF diet and obesity and not simply the obese state.

The Non-Competitive NMDA Antagonist MK-801 Increases Food Intake in Rats

1997 ◽  
Vol 56 (1) ◽  
pp. 145-149 ◽  
Author(s):  
G.A Burns ◽  
R.C Ritter
Keyword(s):  
Food Intake ◽  
Nmda Antagonist ◽  
Mk 801

Cholinergic neurotransmission participates in increased food intake induced by NMDA receptor blockade

2003 ◽  
Vol 285 (3) ◽  
pp. R641-R648 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter ◽  
Gilbert A. Burns
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Motor Neurons ◽  
Nmda Receptor Antagonist ◽  
Sucrose Intake ◽  
Cholinergic Mechanism ◽  
Mk 801 ◽  
Cholinergic Tone

MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, enhances gastric emptying while increasing food intake. Although our previously reported results implicate the vagus in MK-801's effect on feeding, it is not clear whether vagal motor fibers participate in the feeding response. Control of gastric emptying is exerted, in part, by cholinergic vagal motor neurons. Therefore, we examined the ability of MK-801 to increase meal size in the presence or absence of the muscarinic receptor antagonist atropine methyl nitrate. Both central and systemic administration of MK-801 significantly increased intake of 15% sucrose. Intraperitoneal injection of atropine abolished MK-801-induced increase in sucrose intake, whereas administration into the fourth ventricle had no effect. To determine whether augmentation of cholinergic tone produces an enhancement of food intake in the absence of MK-801, we tested the ability of cisapride, a gastric prokinetic agent that promotes acetylcholine release through an action on presynaptic serotonin (5-HT4) receptors, to increase sucrose consumption. Cisapride (500 μg/kg ip) induced a small but significant increase in 15% sucrose intake (15.5 ± 0.5 ml) compared with NaCl (13.0 ± 0.6 ml). Furthermore, when MK-801 (100 μg/kg ip) was given in combination with cisapride, intake was significantly higher (19.8 ± 0.9 ml) than following either agent given alone. Pretreatment with atropine abolished the cisapride-induced increase in intake (12.1 ± 0.9 ml) as well as the increased intake induced by combining MK-801 and cisapride. These results suggest that blockade of NMDA-gated ion channels in the hindbrain increases food intake, in part, via a peripheral muscarinic cholinergic mechanism.

CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying

1990 ◽  
Vol 258 (5) ◽  
pp. R1165-R1169 ◽  
Author(s):  
M. A. Della-Fera ◽  
B. D. Coleman ◽  
C. A. Baile
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gastric Emptying ◽  
Feeding Behavior ◽  
Physiological Role ◽  
Liquid Diet ◽  
Cerebral Ventricles ◽  
Gastric Function ◽  
Sham Feeding ◽  
Gastric Emptying Rate

Cholecystokinin (CCK) released from the intestine during feeding may have a physiological role in satiety. There is also evidence that activation of central CCK-containing pathways is involved in the control of feeding behavior. This study was carried out to determine whether CCK-8 administered into the lateral cerebral ventricles (lv) of rats suppresses both sham feeding (SF) and real feeding (RF). Rats with lv guides and gastric cannulas ate a liquid diet with cannulas open (SF) or closed (RF) after lv (0, 0.05, 0.5 micrograms) or intraperitoneal (ip) (0, 4 micrograms/kg) injection of CCK-8. Both RF and SF were significantly decreased by ip CCK-8. RF was also decreased in a dose-related manner after lv CCK-8, but SF was not affected by lv CCK-8. Decreased feeding after ip CCK-8 may be due in part to its suppression of gastric emptying rate (GER). To determine whether central nervous system (CNS) CCK might also be involved in the control of gastric function, GER was measured after lv (0, 0.05, 0.5 micrograms) or ip (0, 4 micrograms/kg) injection of CCK-8. GER was significantly decreased after ip CCK-8, but lv CCK-8 had no effect on GER. Although both CNS and peripheral CCK peptide systems may be involved in satiety, CNS CCK appears to depend on concurrent peripheral nutrient-related stimuli in eliciting satiety.

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