Partial characterization of a tapeworm-secreted signal factor inducing sustained spike potentials in the smooth muscle of the rat small intestine

The rat tapeworm Hymenolepis diminuta alters the myoelectric activity of the small intestine. To determine if secreted factors from the tapeworm are responsible for these alterations of intestinal smooth muscle activity, tapeworm-conditioned medium (TCM) obtained from in vitro culture was infused via an indwelling cannula into the duodenum of an uninfected rat. Myoelectric recordings were analyzed for sustained spike potentials (SSP) and repetitive bursts of action potentials (RBAP), the previously characterized tapeworm modifications of the normal interdigestive myoelectric pattern. Results indicated that TCM initiated SSP, but not RBAP in the intestine of the uninfected rat. The SSP-inducing signal factor activity, present in TCM, was retained after boiling, prolonged freezing, proteinase treatment, and passage through a 10-kDa exclusion filter. The signal factor was soluble in the aqueous phase on lipid extraction. It was concluded that the SSP-inducing signal factor is a nonproteinaceous, heat-resistant, low-molecular weight, water soluble molecule.     

5-Hydroxytryptamine affects rat migrating myoelectric complexes through different receptor subtypes: evidence from 5-hydroxytryptophan administration

The effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on jejunal migrating myoelectric complexes (MMCs) was investigated in conscious rats. Subcutaneous administration of low doses of 5-HTP (1-2 mg/kg) shortened the period between migrating complexes, whereas high doses of the compound (4-8 mg/kg) disrupted the MMC pattern. The serotonin (5-HT2) antagonist methysergide (8 mg/kg s.c.) did not alter basal MMC, neither did it prevent the effect of a low dose of 5-HTP; conversely, it antagonized the disruption due to the high dose. The 5-HT3 antagonist ICS 205-930 (30 micrograms/kg s.c.) decreased MMC frequency; administration of 2 mg/kg 5-HTP following ICS 205-930 brought the frequency of myoelectric complexes back to basal values. Both effects of 5-HTP were prevented by the decarboxylase inhibitor benserazide (85 mg/kg i.p.), which per se caused a transient inhibition of spiking activity. The results suggest that rat MMCs can be influenced in a composite fashion by progressively increasing concentrations of 5-HT, which in turn activate different receptor subtypes. A peripheral neuronal receptor, probably belonging to the 5-HT3 subclass, mediates the increase in MMC frequency observed after low doses of 5-HTP; higher levels of serotonin activate 5-HT2 receptors, causing disruption of cycling activity. Additionally, 5-HT3 receptors, but not 5-HT2, appear to be relevant for the regulation of the MMC pattern by the endogenous amine.     

Peripheral serotonin dynamics in the rainbow trout (Oncorhynchus mykiss)

Serotonin (5-hydroxytryptamine, 5-HT) occurs in a wide range of tissues throughout the body of the rainbow trout. Results reported here indicate that the main peripheral sources of serotonin are the intestinal tract and the gill epithelium (levels above 1500 ng/g). The high intestinal serotonin concentration is mostly due to serotoninergic nerve fibres, which are present at high density in the intestinal wall. Only about 2% of serotonin is associated with mucosal enterochromaffin cells. In the remaining tissues studied serotonin concentration was below 160 ng/g: the highest concentrations were seen in the anterior and posterior kidneys, followed by the liver, heart, and spleen. 5-Hydroxyindolacetic acid (5-HIAA) levels, except in plasma, were generally lower than serotonin levels, and were below our detection limits in heart, spleen and posterior kidney. Acute d-fenfluramine treatment (5 or 15 mg/kg i.p.) significantly increased 5-HIAA/5-HT ratio in the anterior intestine, pyloric caeca and plasma. Serotonin released from intestinal serotoninergic fibres in response to d-fenfluramine treatment is metabolized locally, and only a small part reaches the blood, from where it can be taken up and metabolized by other peripheral tissues, such as the liver and gill epithelium. The non-metabolized serotonin pool in the blood appears to be located extracellularly, not intracellularly as in mammals. In view of these findings, we present an overview of peripheral serotonin dynamics in rainbow trout.     

Myeloelectric complex of the small intestine and variations in the intestinal motility in sheep]

The motor pattern of the small intestine of the sheep fed ad libitum is characterized by the regular occurrence of myoelectric complexes comprising a phase of regular and irregular spiking activities. Each complex is propagated along the ovine small intestine at a mean velocity of 17 cm/min and originated on the duodenal bulb at 70-100 mn intervals. Reduction and increase in duration of the phase of irregular spiking activity of the complex occurred during fasting and overfeeding respectively. Reduction in spiking activity is paralleled by an increased velocity of propagation whilst a lower migration and a reduced number of the complexes are characteristic of overfeeding. It is concluded that duration, number and velocity of propagation of the myoelectric complexes are adaptative factors in changes of the intestinal flow rate.     

Myoelectric response of the small intestine to the orad presence of the tapeworm Hymenolepis diminuta.

During its 24-hr migratory cycle in the small intestine, Hymenolepis diminuta is located in the orad part of the small intestine during the early morning hours and then in the caudad part of the small intestine during the late afternoon and early evening. During the later period, tapeworm-induced alterations of interdigestive myoelectric activity, a correlate of smooth muscle contraction or intestinal motility, are most intense in the ileal region. The hypothesis tested was that the tapeworm-induced changes in intestinal motility are local responses of the intestine responding to the close proximity of the lumenally positioned tapeworm and to the nutritional state of the host. The small intestine was monitored before and for 20 days after infection using electrodes implanted on the serosa of the small intestine. Myoelectric recordings were analyzed for the frequency of the normal patterns of interdigestive myoelectric spiking patterns and the altered myoelectric spiking related to tapeworm infection. During the morning hours, when the tapeworms are situated in the orad small intestine, no changes were observed during the normal myoelectric pattern of the digestive phase in any region of the intestine. When examined after the conversion of the digestive to interdigestive phase of motility, only on day 10 postinfection was the interdigestive phase significantly altered. It was concluded that the presence of the tapeworm in the orad small intestine during the satiety stage of the rat causes no changes in the electric events of the small intestine, with the exception of day 10 postinfection. Because tapeworms in the orad small intestine do not induce the tapeworm-altered myoelectric activity observed in the afternoon and evening with caudally positioned tapeworms, tapeworm-altered motility is not simply a response of the small intestine to the local presence of the tapeworm.     

Evidence for the Presence of Serotonin Receptors Negatively Coupled to Adenylate Cyclase in the Rabbit Iris-Ciliary Body

Serotonin has no obvious effect on basal cyclic AMP levels but reduces the forskolin-, isoproterenol-, and vasoactive intestinal peptide-induced stimulation of cyclic AMP levels in a dose-dependent manner. Serotonergic, cholinergic, muscarinic, alpha-adrenergic, and dopaminergic antagonists have no effect on the serotonin response. Topical application of a serotonin/pargyline solution to the living eye causes desensitisation of the serotonin response in the iris-ciliary body, an observation confirming the presence of specific serotonergic receptors linked to adenylate cyclase. The 5-HT1A [5-hydroxytryptamine (serotonin) type 1A] receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone mimic the serotonin response in reducing the forskolin-stimulated cyclic AMP levels, as do the indole derivatives 5-methoxytryptamine, 5-hydroxtryptophan, and tryptamine. However, the ineffectiveness of the 5-HT1A agonist ipsapirone and the inability of spiroxatrine to block the serotonin response show that classical 5-HT1A receptors are not involved. The serotonin response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor theophylline, which indicates the involvement of an inhibitory guanine regulatory protein in the coupling of the serotonin receptor to the adenylate cyclase catalytic unit.     

Effects of serotonin on the physiology of the rabbit small intestine

Serotonin has been shown to alter the intestinal transport of ions and intestinal motility. These effects may interfere with each other, modulating the whole physiology of the intestine. We have previously shown that serotonin also alters the transport of nutrients. Thus, the aims of the present work were to determine the possible interference between the secretagogue effect of serotonin and the mechanism by which serotonin inhibits the absorption of nutrients, and to study the effect of serotonin on the digestive activity of nutrients of the brush border membrane jejunum enterocyte in the rabbit. The results show that the secretagogue effect of serotonin neither affects the inhibitory effect of serotonin on the intestinal absorption of the nutrients, nor affects the activity of Na+/K+-ATPase. The activity of sucrase and aminopeptidase N was also not affected by serotonin in the rabbit jejunum. Finally, we also studied different parameters of the motility in the rabbit small intestine. Serotonin seemed to stimulate the motility of the rabbit small intestine by increasing integrated mechanical activity and tone of muscle fibers in duodenum, jejunum, and ileum. In conclusion, serotonin might alter or modulate the whole intestinal physiology.     

Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocin-diabetic rats

Few previous studies have discussed the changes in serotonin receptor activity in the small intestine of diabetic animals. Therefore, we examined serotonin content in duodenal tissue and dose-dependent effects of serotonin agonists and antagonists on the motor activity of ex vivo vascularly perfused duodenum of streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased in enterochromaffin cells but not altered in serotonin-containing neurons in STZ-diabetic rats. Motor activity assessed by frequency, amplitude, and percent motility index per 10 min of pressure waves was reduced in the duodenum of diabetic rats, and this reduction was reversed by insulin treatment. Serotonin dose dependently increased the motor activity in control rat duodenum but only a higher concentration of serotonin increased the motor activity in diabetic rats. The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT(4)) antagonist SB-204070 dose dependently reduced motor activity in both control and diabetic rats, whereas the 5-HT(3) receptor antagonist azasetron, even at a higher concentration, failed to affect motor activity in diabetic rat duodenum but dose dependently reduced motor activity in control rat duodenum. These results suggest that 5-HT(3) receptor activity was impaired but 5-HT(4) receptor activity was intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT(3) receptor activity may induce the motility disturbance in the small intestine of diabetes mellitus.     

Serotonin regulates rhythmic whisking

Many rodents explore their environment by rhythmically palpating objects with their mystacial whiskers. These rhythmic whisker movements ("whisking"; 5-9 Hz) are thought to be regulated by an unknown brainstem central pattern generator (CPG). We tested the hypothesis that serotonin (5-HT) inputs to whisking facial motoneurons (wFMNs) are part of this CPG. In response to exogenous serotonin, wFMNs recorded in vitro fire rhythmically at whisking frequencies, and selective 5-HT2 or 5-HT3 receptor antagonists suppress this rhythmic firing. In vivo, stimulation of brainstem serotonergic raphe nuclei evokes whisker movements. Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements. These findings suggest that serotonin is both necessary and sufficient to generate rhythmic whisker movements and that serotonergic premotoneurons are part of a whisking CPG.     

Serotonin enhances beta-endorphin secretion to lower plasma glucose in streptozotocin-induced diabetic rats

Although serotonin, serotonin uptake inhibitors and serotonin precursors (including tryptophan or 5-hydroxytryptophan) are known to have hypoglycemic action in rodents or human, it is not clear whether serotonin has hypoglycemic effect in streptozotocin-induced diabetic rats (STZ-diabetic rats). The aim of this study was to investigate the action of serotonin in regulating the plasma glucose STZ-diabetic rats. Plasma glucose, insulin, beta-endorphin and adrenaline were assessed after intraperitoneal administration of serotonin. Serotonin produced hypoglycemic effects without altering plasma insulin and adrenaline levels but increasing beta-endorphin level in STZ-diabetic rats. The glycogen content in soleus muscle was increased at 90 min after application of serotonin (0.3 mg/kg) in STZ-diabetic rats. Dihydroergotamine (non-selective 5-HT receptor blocker) and pimozide (5-HT(7) receptor blocker) abolished the hypoglycemic effect of serotonin in STZ-diabetic rats. Serotonin-induced hypoglycemic effect in association with the increase of beta-endorphin release was abolished in bilaterally adrenalectomized STZ-diabetic rats. In isolated adrenal gland of STZ-diabetic rats, the increase of beta-endorphin secretion in response to serotonin was reduced by either dihydroergotamine or pimozide. Pretreatment with naloxone (1.0 mg/kg, i.p.) prevented serotonin-induced plasma glucose lowering effect in STZ-diabetic rats. The results demonstrated that serotonin may activate 5-HT(7) receptor on rat adrenal gland to enhance of beta-endorphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats.     

Docosahexaenoyl serotonin emerges as most potent inhibitor of IL-17 and CCL-20 released by blood mononuclear cells from a series of N-acyl serotonins identified in human intestinal tissue

Fatty acid amides (FAAs), conjugates of fatty acids with ethanolamine, mono-amine neurotransmitters or amino acids are a class of molecules that display diverse functional roles in different cells and tissues. Recently we reported that one of the serotonin-fatty acid conjugates, docosahexaenoyl serotonin (DHA-5-HT), previously found in gut tissue of mouse and pig, attenuates the IL-23-IL-17 signaling axis in LPS-stimulated mice macrophages. However, its presence and effects in humans remained to be elucidated. Here, we report for the first time its identification in human intestinal (colon) tissue, along with a series of related N-acyl serotonins. Furthermore, we tested these fatty acid conjugates for their ability to inhibit the release of IL-17 and CCL-20 by stimulated human peripheral blood mononuclear cells (PBMCs). Serotonin conjugates with palmitic acid (PA-5-HT), stearic acid (SA-5-HT) and oleic acid (OA-5-HT) were detected in higher levels than arachidonoyl serotonin (AA-5-HT) and DHA-5-HT, while eicosapentaenoyl serotonin (EPA-5-HT) could not be quantified. Among these, DHA-5-HT was the most potent in inhibiting IL-17 and CCL-20, typical Th17 pro-inflammatory mediators, by Concanavalin A (ConA)-stimulated human PBMCs. These results underline the idea that DHA-5-HT is a gut-specific endogenously produced mediator with the capacity to modulate the IL-17/Th17 signaling response. Our findings may be of relevance in relation to intestinal inflammatory diseases like Crohn's disease and Ulcerative colitis.     

Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod

The intestinal peristaltic reflex induced by mucosal stimulation is mediated by mucosal release of serotonin (5-HT), which acts on 5-HT(4) receptors located on CGRP-containing afferent nerve terminals. Exposure of the colonic mucosa to the 5-HT(4) receptor agonist tegaserod in the range of 1 nM to 10 muM elicits a peristaltic reflex and stimulates colonic propulsion. The present study was designed to identify the 5-HT(4) receptor subtype mediating the reflex and determine whether functionally effective concentrations of tegaserod desensitize the reflex induced by mucosal stimulation. Exposure of rat colonic mucosa to tegaserod in the range of 5 nM to 5 muM for 5 or 10 min caused rapid time- and concentration-dependent desensitization of the peristaltic reflex induced by mucosal stroking, consistent with the operation of a rapidly desensitizing 5-HT(4b) receptor subtype. Desensitization was accompanied by a decrease in CGRP release. The rate of recovery of peristaltic response depended on the desensitizing concentration of tegaserod: ascending contraction and descending relaxation recovered within 15 min after 5-50 nM tegaserod, 30 min after 0.5 muM, and 60 min after 5 muM. Neither CGRP release nor the peristaltic reflex induced by muscle stretch was affected by 5-HT(4) receptor desensitization, providing further evidence that 5-HT does not mediate the reflex induced by muscle stretch. These results suggest in cases of increased 5-HT availability or prolonged exposure, such as colitis, that it is likely the peristaltic reflex will be blunted.     

GLP-1 and GLP-2 act in concert to inhibit fasted,but not fed,small bowel motility in the rat

Small bowel motility was studied in rats at increasing (1-20 pmol/kg/min) intravenous doses of either glucagon-like peptide-1 (GLP-1) or glucagon-like peptide-2 (GLP-2) alone, or in combination in the fasted and fed state. There was a dose-dependent inhibitory action of GLP-1 on the migrating myoelectric complex (MMC), where the dose of 5 pmol/kg/min induced an increased MMC cycle length. No effect was seen with GLP-2 alone, but the combination of GLP-1 and GLP-2 induced a more pronounced inhibitory effect, with significant increase of the MMC cycle length from a dose of 2 pmol/kg/min. During fed motility, infusion of GLP-1 resulted in an inhibition of spiking activity compared to control. In contrast, infusion of GLP-2 only numerically increased spiking activity compared to control, while the combination of GLP-1 and GLP-2 resulted in no change compared to control. In summary, this study demonstrates an additive effect of peripheral administration of GLP-1 and GLP-2 on fasted small bowel motility. In the fed state, GLP-1 and GLP-2 seem to display counter-balancing effects on motility of the small intestine.     

The myoelectrical activity of the gastroduodenal area in ulcer formation due to serotonin

The effects of prolonged subcutaneous administration of serotonin on the myoelectric activity of the gastroduodenal junction were investigated in conscious rabbits. Serotonin produced the duodenogastric discoordination by increasing duodenal activity and decreasing the activity of stomach and pylorus. This discoordination resulted in gastric ulceration. Atropine prevented both duodenogastric discoordination and ulceration. These results indicate that serotonin ulceration is related to duodenogastric discoordination.     

Changes in colonic myoelectric spiking activity during stimulation by bisacodyl

The purpose of this study was to determine some relationships between colonic myoelectric spiking activity and intraluminal propulsion when colonic peristalsis was stimulated by bisacodyl. Myoelectric recordings were obtained in 12 subjects by means of a 50 cm long Silastic tube equipped with four bipolar electrodes fixed at 10-cm intervals. The tube was introduced into the left colon by flexible sigmoidoscopy and the electrodes were located at 50, 40, 30, and 20 cm from the anal verge. A small polyethylene catheter opening at the proximal end of the Silastic tube was used for introducing the laxative into the colon. One hour recording sessions were obtained before and after bisacodyl administration (5 mL of 0.4% solution). The control tracings showed that colonic spiking activity was made of rhythmic stationary bursts that occurred at only one electrode site and of sporadic bursts that were either propagating over the whole colonic segment or nonpropagating. Administration of bisacodyl was followed by complete suppression of the rhythmic stationary activity; a considerable increase in the sporadic spiking activity, propagating as well as nonpropagating; the occurrence of abdominal cramps and urgency to defecate, both associated with the propagating sporadic spike bursts. It is concluded that colonic propulsion induced by bisacodyl may be dependent upon the production of the sporadic bursts, particularly the propagating ones, while the rhythmic stationary bursts do not seem to play a significant role in colonic transit.     

Chemosensitivity of the rat type I slowly adapting mechanoreceptor

An in vitro lateral thoracic skin preparation of the adult rat was used to test the effect of serotonin (5, 50, 500 microM) and control solutions on the response of the type I slowly adapting mechanoreceptor to a standard mechanical stimulus. Serotonin (5-HT) significantly increased the magnitude of the type I response to mechanical indentation: 50 microM 5-HT infusion enhanced responsiveness more effectively than 5 microM 5-HT. In the absence of mechanical stimulation, little or no change in spontaneous discharge relative to control was observed, and recovery to baseline levels occurred within three stimulus trials. In vitro and in vivo control experiments showed no statistically significant change in responsiveness over a similar number of stimulus cycles. It was concluded that 5-HT modulates, but does not activate the rat type I receptor or alter its ability to encode the depth and/or velocity of mechanical displacement. Copyright Copyright 1999 S. Karger AG, Basel     

Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine

Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC), a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking) interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.     

Involvement of c-Src and protein kinase C delta in the inhibition of Cl(-)/OH- exchange activity in Caco-2 cells by serotonin

Serotonin (5-hydroxytryptamine (5-HT)) is an important neurotransmitter and intercellular messenger regulating various gastrointestinal functions, including electrolyte transport. To date, however, no information is available with respect to its effects on the human intestinal apical anion exchanger Cl(-)/OH- (HCO3-). The present studies were therefore undertaken to examine the direct effects of serotonin on OH- gradient-driven 4,4'-diisothiocyanato-stilbene-2, 2'-disulfonic acid-sensitive 36Cl- uptake utilizing the post-confluent transformed human intestinal epithelial cell line Caco-2. Our results demonstrate that serotonin inhibits Cl(-)/OH- exchange activity in Caco-2 cells via both tyrosine kinase and Ca(2+)-independent protein kinase C delta-mediated pathways involving either 5-HT3 or 5-HT4 receptor subtype. The data consistent with our inference are as follows. (i) The short term treatment of cells with 5-HT (0.1 microM) for 15-60 min significantly decreased Cl(-)/OH- exchange (50-70%, p < 0.05). (ii) The specific agonists for 5-HT3, m-chlorophenylbiguanide, and 5-HT4, 3-(4-allylpiperazin-1-yl)-2-quinoxaline chloronitrile, mimicked the effects of serotonin. (iii) Tropisetron dual inhibitor for both the 5-HT3/4 receptor subtypes significantly blocked the inhibition, whereas specific 5-HT3 (Y-25130) or 5-HT4 receptor (RS39604) antagonist failed to block the inhibitory effects of 5-HT. (iv) The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl ester) had no effect on the serotonin-induced inhibition. (v) The specific protein kinase C (PKC) inhibitors chelerythrine chloride or calphostin C completely blocked the inhibition by 5-HT. (vi) The specific inhibitor for PKC delta, rottlerin, significantly blocked the inhibition by 5-HT. (vii) The specific tyrosine kinase inhibitor, herbimycin, or Src family kinase inhibitor, PP1, abolished the 5-HT-mediated inhibition of Cl(-)/OH- exchange activity. (viii) 5-HT stimulated tyrosine phosphorylation of c-Src kinase and PKC delta.     

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

Several gastrointestinal stimuli, including some intestinal nutrients, have been shown to exert their satiating effect via activation of serotonin type-3 (5-HT(3)) receptors. The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT(3) receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT(3) receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT(3) receptor activation. Rats duodenally infused with 72 and 130 mM Intralipid suppressed 1-h 15% sucrose intake by 33 and 67%, respectively. Suppression of sucrose intake by 72 mM Intralipid was significantly attenuated by ondansetron at all doses tested (0.5, 1.0, 2.0, and 5.0 mg/kg ip), whereas the lowest effective dose of ondansetron to attenuate suppression of intake by 130 mM Intralipid was 1.0 mg/kg. Furthermore, infusion of 130 mM Intralipid suppressed 1- and 4-h chow intake by 35 and 20%, respectively. Ondansetron administered as low as 0.5 mg/kg significantly attenuated 1-h Intralipid-induced suppression of chow intake and completely reversed the suppression by 4 h. Administration of ondansetron alone did not alter sucrose or chow intake compared with vehicle injection at any time. Finally, to test whether Intralipid-induced neuronal activation of the dorsal vagal complex is mediated by 5-HT(3) receptors, Fos-like immunoreactivity (Fos-LI) was quantified in ondansetron-pretreated rats following intestinal lipid infusion. Ondansetron (1 mg/kg) significantly attenuated duodenal intralipid-induced Fos-LI in the dorsal hindbrain. These data support the hypothesis that 5-HT(3) receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids.