The food contaminant mycotoxin deoxynivalenol inhibits the swallowing reflex in anaesthetized rats

Deoxynivalenol (DON), one of the most abundant mycotoxins found on cereals, is known to be implicated in acute and chronic illnesses in both humans and animals. Among the symptoms, anorexia, reduction of weight gain and decreased nutrition efficiency were described, but the mechanisms underlying these effects on feeding behavior are not yet totally understood. Swallowing is a major motor component of ingestive behavior which allows the propulsion of the alimentary bolus from the mouth to the esophagus. To better understand DON effects on ingestive behaviour, we have studied its effects on rhythmic swallowing in the rat, after intravenous and central administration. Repetitive electrical stimulation of the superior laryngeal nerve or of the tractus solitarius, induces rhythmic swallowing that can be recorded using electromyographic electrodes inserted in sublingual muscles. Here we provide the first demonstration that, after intravenous and central administration, DON strongly inhibits the swallowing reflex with a short latency and in a dose dependent manner. Moreover, using c-Fos staining, a strong neuronal activation was observed in the solitary tract nucleus which contains the central pattern generator of swallowing and in the area postrema after DON intravenous injection. Our data show that DON modifies swallowing and interferes with central neuronal networks dedicated to food intake regulation

Réflexes somato-sympathiques et motricité colo-sphincterienne (étude chez le chat et chez l'homme)

AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Evidence for supraspinal nervous control of external anal sphincter motility in the cat

International audienceThe aim of this study was to investigate the role of noradrenergic descending nervous pathways in external anal sphincter motility. Forthis purpose, the effects of intravenously injected adrenoceptor antagonist and agonist on the tonic electrical activity of this sphincter were studied in anesthetized cats. The effects of stimulating the region of the locus coeruleus and the effects of intravenous, intracerebroventricular and intrathecal injection of the above drugs on the electromyographic responses of this muscle to pudendal nerve stimulation were also investigated. The tonic sphincteric activity and the reflex response triggered by electrically stimulating pudendal afferent nerve fibers were inhibited by alpha1-adrenoceptor antagonist nicergoline and enhanced by alpha1-adrenoceptor agonist phenylephrine. Stimulation of the locus coeruleus area either inhibited or enhanced the reflex responses. Intracerebroventricular and intrathecal injection of the alpha2-adrenoceptor agonists, morphine and leu-enkephalin decreased the amplitude of these reflex responses. All the effects of opioids were blocked by naloxone and by spinalization performed at the cervical and lumbar levels. The direct response elicited by stimulating the sphincteric motor axons was not affected either by these drugs or by the brainstem stimulation. These results suggests the existence of a pontine neuronal network controlling the motility of the external anal sphincter via noradrenergic and opioid neurons

In vivo study of the role of muscarinic receptors in the parasympathetic control of rabbit colonic motility

International audienceThe aim of the present study was to elucidate the role of the non-M1 muscarinic receptors, in the extrinsic and intrinsic nerve control of in vivo colonic motility. Experiments were performed on the proximal colon of anaesthetized rabbits. In this species, the parasympathetic innervation of the proximal colon originates from the vagus nerves. The action of methoctramine and 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP) was studied on excitatory junction potentials (EJPs), and on inhibitory junction potentials (IJPs) elicited in smooth muscle cells by stimulating parasympathetic efferents. The effects of the same drugs on spontaneous spiking activity were also investigated. The EJPs either decreased or disappeared after intra-arterial (i.a.) administration of 4-DAMP (45 pg to 450 ng). In the presence of 4-DAMP, further intravenous (i.v.) administration of pirenzepine (0.1 mg.kg-1) had facilitatory effects on the inhibitory pathway, i.e., after abolition of the EJPs, vagal stimulation elicited IJPs. With the highest dose of 4-DAMP, vagal stimulation immediately elicited IJPs the amplitude of which still increased after pirenzepine. In the presence of 4-DAMP, the spontaneous spike discharge was not noticeably altered. Methoctramine (0.37 to 75 micrograms, i.a. or 50 micrograms to 0.2 mg.kg-1, i.v.) increased the amplitude of the EJPs, whereas it decreased that of the IJPs. In addition, at the same doses, it either initiated or increased spike discharges that were not altered by pirenzepine up to 0.2 mg.kg-1, i.v. The so-called rebound excitation occurring after IJPs was not affected by methoctramine. No change in the EJP or IJP amplitude was observed with gallamine at sufficiently high doses to paralyse striated muscles (up to 3 mg.kg-1.h-1). It is concluded that the parasympathetic excitatory pathway to smooth muscle is blocked by 4-DAMP, whereas it is facilitated by methoctramine. 4-DAMP has no effect on the inhibitory pathway which is strongly depressed by methoctramine; however, the fact that these two drugs have opposite effects indicates that 4-DAMP and methoctramine may act on different muscarinic receptor subtypes. In addition, the facilitatory effects of pirenzepine on IJPs observed in animals pre-treated with 4-DAMP, indicates that the latter drug may act on non-M1 and non-M2 (presumably M3) muscarinic receptors. Methoctramine acts on non-M1 and non-M3 (presumably M2) receptors. The spike discharge induced by methoctramine is presumably due to an increased release of acetylcholine, and possibly also of a non-cholinergic transmitter which has excitatory effects on smooth muscle, the identification of which requires further investigations. The inhibitory effects of methoctramine on IJPs indicate that non-adrenergic non-cholinergic (NANC) neurones which are inhibitory of smooth muscle are controlled by inhibitory intramural neurones, the activity of which is expressed through a muscarinic mechanism involving non-M1 and non-M3, presumably M 2 receptor

Effects of leptin on cat intestinal motility

In a previous study, we established that leptin controls food intake and immune responses by acting on intestinal vagal chemosensitive mechanoreceptors via a functional link with interleukin-1β (Il-1β). Since the control of intestinal motility is one of the main roles of the vagal afferent fibres, we investigated the effects of leptin on intestinal electromyographic (EMG) activity which reflects intestinal motility. For this purpose, the effects of locally injected leptin on small intestine spontaneous EMG activity were studied in 23 anaesthetised cats. The EMG activity was recorded using bipolar electrodes implanted in the proximal small intestine. Leptin and Il-1β (0.1, 1 and 10 μg), administered through the artery irrigating the upper part of the intestine 20 min after cholecystokinin (CCK, 10 μg, i.a.), had significant (P < 0.001) excitatory effects on intestinal EMG activity. The effects of both substances were blocked by the endogenous interleukin-1β receptor antagonist (Il-1ra, 250 μg, i.a.), by atropine (250 μg, i.a.) and by vagotomy. In the absence of CCK, leptin and Il-1β had no effect on intestinal electrical activity. It can therefore be concluded that: (1) leptin is effective only after the previous intervention of CCK, (2) the enhancement of the electrical activity induced by leptin involves Il-1β receptors and the cholinergic excitatory pathway, (3) the modes whereby the leptin-induced enhancement of EMG activity occurs strongly suggest that these effects are due to a long-loop reflex involving intestinal vagal afferent fibres and the parasympathetic nervous system

Effects of Stimulation of Vesical Afferents on Colonic Motility in Cats

International audienceThe effects of distension and isovolumetric contraction of urinary bladder on colonic motility were studied in anesthetized cats. Distension and contraction of the urinary bladder induced an inhibition of spontaneous colonic electromyographic activity and a decrease in the amplitudes of the excitatory junction potentials evoked in the colon by stimulation of the distal end of the parasympathetic nerve fibers. This inhibition was blocked by guanethidine and phentolamine. Reversely, vesical emptying resulted in an increase in colonic motility, abolished by atropine, and an increase in the amplitude of the excitatory junction potentials. Both excitatory and inhibitory reflexes disappeared after hexamethonium. The inhibitory effects of bladder distension were abolished by bilateral section of the lumbar ventral or dorsal spinal roots and after bilateral section of the lumbar colonic or hypogastric nerves. These results indicate (a) that the vesical afferents responsible for the inhibitory and excitatory reflexes run in the hypogastric and pelvic nerves respectively and (b) that the inhibitory and excitatory effects are caused by the activation of sympathetic and parasympathetic efferent nerve fibers, respectively. The supraspinal nervous structures were not implicated in these reflexes because they persisted in spinal cats

Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli

International audienceBackground: Alverine citrate is commonly used in the treatment of painful affections of the colon.Aim: To determine whether alverine citrate acts on the vagal sensory endings.Methods: Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied.Results: The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5±10 lg/kg), substance P (5± 10 lg/kg) or phenylbiguanide (5±10 lg/kg), a 5-HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present.Conclusions: Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti-spasmodic effects

Supraspinal control of external anal sphincter motility: effects of vesical distension in humans and cats

International audienceA pontine centre located near the micturition centre controlling external anal sphincter (EAS) motility via noradrenergic neurones has been described in cats. The aim of this study was to determine (i) whether a similar centre controls EAS motility in humans and (ii) whether this centre is involved in vesico-sphincteric reflexes in cats and humans. The effects of an alpha-1-adrenoceptor antagonist (nicergoline) and those of vesical distension on the electrical activity of the EAS were studied in paraplegic and non-paraplegic volunteers. The effects of vesical distension by injecting saline at physiological levels on the responses of the EAS to pudendal nerve stimulation were investigated in intact cats and cats with nerve sections. In non-paraplegic subjects, nicergoline and vesical distension abolished the activity of the EAS. These effects were no longer observed in paraplegic patients. In cats, vesical distension inhibited the reflex response of the EAS to pudendal nerve stimulation. This vesico-sphincteric reflex, which was no longer observed in spinal animals, persisted after nicergoline injection. These findings indicate that in humans, there exists a supraspinal centre facilitating the tonic activity of the EAS via noradrenergic neurones not involved in the inhibitory vesico-sphincteric reflex

The Food Contaminant Mycotoxin Deoxynivalenol Inhibits the Swallowing Reflex in Anaesthetized Rats

International audienceDeoxynivalenol (DON), one of the most abundant mycotoxins found on cereals, is known to be implicated in acute and chronic illnesses in both humans and animals. Among the symptoms, anorexia, reduction of weight gain and decreased nutrition efficiency were described, but the mechanisms underlying these effects on feeding behavior are not yet totally understood. Swallowing is a major motor component of ingestive behavior which allows the propulsion of the alimentary bolus from the mouth to the esophagus. To better understand DON effects on ingestive behaviour, we have studied its effects on rhythmic swallowing in the rat, after intravenous and central administration. Repetitive electrical stimulation of the superior laryngeal nerve or of the tractus solitarius, induces rhythmic swallowing that can be recorded using electromyographic electrodes inserted in sublingual muscles. Here we provide the first demonstration that, after intravenous and central administration, DON strongly inhibits the swallowing reflex with a short latency and in a dose dependent manner. Moreover, using c-Fos staining, a strong neuronal activation was observed in the solitary tract nucleus which contains the central pattern generator of swallowing and in the area postrema after DON intravenous injection. Our data show that DON modifies swallowing and interferes with central neuronal networks dedicated to food intake regulation

Colonosphincteric electromyographic responses to sacral root stimulation: evidence for a somatosympathetic reflex.

International audienceThe aim of the present study was to determine the effects of selectively stimulating the afferent fibres running in the dorsal sacral roots (S1, S2, S3) and the somatic (radial and sciatic) nerves on colonic and internal anal sphincter (IAS) electromyographic (EMG) activity in anaesthetized cats to try to understand how sacral nerve stimulation can improve fecal continence in human. Electrically stimulating the afferent fibres present in the sacral dorsal roots and somatic nerves inhibited the colonic spike potential frequency (n = 97) and increased the slow variations in the sphincteric membrane potential (n = 76). These effects were found to have disappeared after administering an alpha-noradrenergic receptor blocker (n = 64) or sectioning the sympathetic efferent fibres innervating these organs (n = 69) suggesting the involvement of the sympathetic system in the effects observed. Moreover, no significant differences were observed between the effects of sacral dorsal root vs somatic nerve stimulation on colonic and sphincteric EMG activity. In conclusion, the data obtained here show that neurostimulation applied to the sacral spinal roots may improve fecal continence by inhibiting colonic activity and enhancing IAS activity via a somatosympathetic reflex