Gastric distension-induced c-fos expression in catecholaminergic neurons of rat dorsal vagal complex

1997 ◽  
Vol 272 (1) ◽  
pp. R59-R67 ◽  
Author(s):  
A. E. Willing ◽  
H. R. Berthoud
Keyword(s):  
Large Degree ◽  
Second Order ◽  
Vagal Afferents ◽  
Gastric Distension ◽  
Minor Role ◽  
High Threshold ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Fos Expression ◽  
Degree Of Convergence

Functionally specific vagal afferents were stimulated by gastric balloon distension in unanesthetized rats, followed by double c-fos/dopamine beta-hydroxylase (DBH) immunocytochemistry, to identify second-order neurons in the dorsal vagal complex. Continuous and repeated phasic distension with similar volumes produced similar numbers and patterns of c-fos expression, with most of the activated neurons in the medial and commissural nucleus of the solitary tract (NTS) and dorsal motor nucleus (DMNX). Larger distension activated significantly more neurons in all responsive areas but there was no differential effect. In most NTS subnuclei and the DMNX, a small (3-5%) proportion of gastric distension-activated neurons was DBH-immunoreactive (DBH-IR), and this proportion did not significantly change with type of distension. With continuous and repeated small distensions, 10-12% and, with the large distension, 22-30% of all DBH-IR neurons expressed c-fos. The results suggest a large degree of convergence between rapidly adapting mucosal receptors and slowly adapting tension receptors, but not between low- and high-threshold tension receptors, and a relatively minor role of catecholaminergic second-order neurons in the dissemination of distension signals in the brain.

CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

2005 ◽  
Vol 289 (3) ◽  
pp. R695-R703 ◽  
Author(s):  
E. H. E. M. van de Wall ◽  
P. Duffy ◽  
R. C. Ritter
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Solitary Tract ◽  
C Fibers ◽  
Balloon Distension ◽  
Electrophysiological Responses ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Afferent Response ◽  
And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
Author(s):  
Marja D. Van Sickle ◽  
Lorraine D. Oland ◽  
Ken Mackie ◽  
Joseph S. Davison ◽  
Keith A. Sharkey
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Area Postrema ◽  
Motor Nucleus ◽  
Cb1 Receptors ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Site Of Action ◽  
Fos Expression ◽  
The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

scholarly journals Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

1999 ◽  
Vol 277 (4) ◽  
pp. R1104-R1111 ◽  
Author(s):  
Huiyuan Zheng ◽  
Lisa Kelly ◽  
Laurel M. Patterson ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Nmda Receptor ◽  
Area Postrema ◽  
Additive Model ◽  
Nmda Receptor Antagonist ◽  
Gastric Distension ◽  
Motor Nucleus ◽  
Sucrose Intake ◽  
Mk 801 ◽  
Dorsal Motor Nucleus ◽  
Fos Expression

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.

Medullary c-Fos activation in rats after ingestion of a satiating meal

1998 ◽  
Vol 275 (1) ◽  
pp. R262-R268 ◽  
Author(s):  
L. Rinaman ◽  
E. A. Baker ◽  
G. E. Hoffman ◽  
E. M. Stricker ◽  
J. G. Verbalis
Keyword(s):  
Area Postrema ◽  
Vagal Afferents ◽  
Early Gene ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Neural Activation ◽  
Food Ingestion ◽  
Catecholaminergic Neurons ◽  
Medial Nucleus ◽  
Fos Expression

The distribution and chemical phenotypes of hindbrain neurons that are activated in rats after food ingestion were examined. Rats were anesthetized and perfused with fixative 30 min after the end of 1-h meals of an unrestricted or rationed amount of food, or after no meal. Brain sections were processed for localization of the immediate-early gene product c-Fos, a marker of stimulus-induced neural activation. Hindbrain c-Fos expression was low in rats that ate a rationed meal or no meal. Conversely, c-Fos was prominent in the medial nucleus of the solitary tract (NST) and area postrema in rats that ate to satiety. There was a significant positive correlation between postmortem weight of gastric contents and the proportion of NST catecholaminergic neurons expressing c-Fos. Cells in the ventrolateral medulla (VLM) were not activated in rats after food ingestion, in contrast with previous findings that stimulation of gastric vagal afferents with anorexigenic doses of cholecystokinin activates c-Fos expression in both NST and VLM catecholaminergic cells. These findings indicate that anatomically distinct subsets of hindbrain catecholaminergic neurons are activated in rats after food ingestion and that activation of these cells is quantitatively related to the magnitude of feeding-induced gastric distension.

Neurons in the dorsal motor nucleus of the vagus may integrate vagal and spinal information from the GI tract

1995 ◽  
Vol 268 (5) ◽  
pp. G780-G790 ◽  
Author(s):  
W. E. Renehan ◽  
X. Zhang ◽  
W. H. Beierwaltes ◽  
R. Fogel
Keyword(s):  
Brain Stem ◽  
Vagal Afferents ◽  
High Threshold ◽  
Motor Nucleus ◽  
Potential Contribution ◽  
Gi Tract ◽  
Dorsal Motor Nucleus ◽  
Efferent Neurons ◽  
Spinal Afferents ◽  
The Brain

Previous investigations have provided evidence that the activity of parasympathetic efferent neurons in the dorsal motor nucleus of the vagus (DMNV) may be influenced by either vagal afferent or spinal input from the gastrointestinal (GI) tract. Many questions remain, however, regarding the nature of this input and its integration by the brain stem. The present study was designed to examine one important aspect of this issue: the potential contribution of the spinal input to the brain stem in the generation of the response properties of intestine-sensitive neurons in the DMNV. Using intracellular recording and labeling techniques in adult rats, we found that ascending spinal pathways were capable of conveying both low- and high-threshold visceral information to the DMNV. We also determined that the neurons in the nucleus of the solitary tract failed to respond to intestinal distention when the vagal afferents to the brain stem had been severed, suggesting that the spinal projections terminate directly on the DMNV neurons. These data lend support to the emerging hypothesis that the spinal afferents that accompany the abdominal splanchnics are capable of responding to both innocuous and noxious stimuli. The results also suggest that the neurons in the DMNV play a larger role in the integration of visceral sensory information than was previously realized.

scholarly journals The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Cryptotis parva)

2021 ◽  
Vol 12 ◽  
Author(s):  
W. Zhong ◽  
N. A. Darmani
Keyword(s):  
Channel Blocker ◽  
Tryptophan Hydroxylase ◽  
Nucleus Tractus Solitarius ◽  
Transient Receptor Potential Vanilloid ◽  
Motor Nucleus ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Hcn Channel ◽  
Serotonin Neurons ◽  
Fos Expression

Subtypes (1–4) of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the central and peripheral nervous systems, as well as the cells of smooth muscles in many organs. They mainly serve to regulate cellular excitability in these tissues. The HCN channel blocker ZD7288 has been shown to reduce apomorphine-induced conditioned taste aversion on saccharin preference in rats suggesting potential antinausea/antiemetic effects. Currently, in the least shew model of emesis we find that ZD7288 induces vomiting in a dose-dependent manner, with maximal efficacies of 100% at 1 mg/kg (i.p.) and 83.3% at 10 µg (i.c.v.). HCN channel subtype (1–4) expression was assessed using immunohistochemistry in the least shrew brainstem dorsal vagal complex (DVC) containing the emetic nuclei (area postrema (AP), nucleus tractus solitarius and dorsal motor nucleus of the vagus). Highly enriched HCN1 and HCN4 subtypes are present in the AP. A 1 mg/kg (i.p.) dose of ZD7288 strongly evoked c-Fos expression and ERK1/2 phosphorylation in the shrew brainstem DVC, but not in the in the enteric nervous system in the jejunum, suggesting a central contribution to the evoked vomiting. The ZD7288-evoked c-Fos expression exclusively occurred in tryptophan hydroxylase 2-positive serotonin neurons of the dorsal vagal complex, indicating activation of serotonin neurons may contribute to ZD7288-induced vomiting. To reveal its mechanism(s) of emetic action, we evaluated the efficacy of diverse antiemetics against ZD7288-evoked vomiting including the antagonists/inhibitors of: ERK1/2 (U0126), L-type Ca2+ channel (nifedipine); store-operated Ca2+ entry (MRS 1845); T-type Ca2+ channel (Z944), IP3R (2-APB), RyR receptor (dantrolene); the serotoninergic type 3 receptor (palonosetron); neurokinin 1 receptor (netupitant), dopamine type 2 receptor (sulpride), and the transient receptor potential vanilloid 1 receptor agonist, resiniferatoxin. All tested antiemetics except sulpride attenuated ZD7288-evoked vomiting to varying degrees. In sum, ZD7288 has emetic potential mainly via central mechanisms, a process which involves Ca2+ signaling and several emetic receptors. HCN channel blockers have been reported to have emetic potential in the clinic since they are currently used/investigated as therapeutic candidates for cancer therapy related- or unrelated-heart failure, pain, and cognitive impairment.

scholarly journals The Neural Pathway of Reflex Regulation of Electroacupuncture at Orofacial Acupoints on Gastric Functions in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jianhua Liu ◽  
Wenbin Fu ◽  
Wei Yi ◽  
Zhenhua Xu ◽  
Nenggui Xu
Keyword(s):  
Myoelectric Activity ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Neural Pathway ◽  
Excitatory Effect ◽  
Reflex Regulation ◽  
Gastric Myoelectric Activity ◽  
Dorsal Motor Nucleus ◽  
Spike Bursts

Acupuncture has a reflex regulation in gastrointestinal functions, which is characterized with segment. In the present study, the neural pathway of electroacupuncture (EA) at orofacial acupoints (ST2) on gastric myoelectric activity (GMA) in rats was investigated. The results indicated that EA at ST2 facilitated spike bursts of GMA, which is similar to EA at limbs and opposite to EA at abdomen. The excitatory effect was abolished by the transaction of infraorbital nerves, dorsal vagal complex lesion, and vagotomy, respectively. In addition, microinjection of L-glutamate into the nucleus of the solitary tract (NTS) attenuated the excitatory effect. All these data suggest that the dorsal vagal complex is involved in the reflex regulation of EA at orofacial acupoints on gastric functions and NTS-dorsal motor nucleus of the vagus (DMV) inhibitory connections may be essential for it.

Physiological enteric stimulation elicits cardiovascular reflexes in the rat

1988 ◽  
Vol 255 (3) ◽  
pp. G319-G328 ◽  
Author(s):  
B. S. Pittam ◽  
W. R. Ewart ◽  
F. Appia ◽  
D. L. Wingate
Keyword(s):  
Portal Vein ◽  
Pressor Response ◽  
Vagal Afferents ◽  
Gastric Distension ◽  
Cardiovascular Reflexes ◽  
Central Processing ◽  
Hepatic Portal Vein ◽  
The Mean ◽  
Hepatic Portal ◽  
Portal Vein Infusion

By use of anesthetized rats, parameters for the activation of cardiovascular reflexes by stimulation of gastric or hepatic receptors have been established. For reflex activation, the mean minimum intragastric volume was 4 ml, and the mean minimum rate of hepatic portal vein infusion was 0.3 ml/min. Subdiaphragmatic vagotomy affected the response to gastric distension but did not appear to affect the response to hepatic portal vein infusion, indicating that vagal afferents are involved in mediating gastric-cardiovascular but not hepatic-cardiovascular reflexes. Experiments designed to emphasize the vagal component of the response to gastric distension confirmed this finding. Antagonist effects indicated that the tachycardia was mediated by beta-adrenoreceptor stimulation and that the pressor response was mainly mediated by alpha-adrenoreceptors. The data show that stimuli used in experiments to assess central processing of sensory information from the gastrointestinal tract can activate cardiovascular reflexes. Caution in the design of such experiments and in the interpretation of the data generated is indicated.

CART in the dorsal vagal complex: sources of immunoreactivity and effects on Fos expression and food intake

2002 ◽  
Vol 957 (2) ◽  
pp. 298-310 ◽  
Author(s):  
Huiyuan Zheng ◽  
Laurel M Patterson ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Food Intake ◽  
Dorsal Vagal Complex ◽  
Fos Expression
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