Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs

Koga, Tomoshige; Fukuda, Hiroyuki

doi:10.1016/0168-0102(92)90078-q

Cited by 81 publications

(39 citation statements)

References 33 publications

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“…Brainstem SP has been implicated in autonomic control [16,29] and in control of emetic reflexes [41,46,48]. Of greatest relevance to the current use of C. parva as a small-animal emesis model, SP was found in the brainstem areas held to be key mediators of the emetic reflex: The area postrema, solitary tract and nucleus, and dorsal motor nucleus of the vagus nerve [4,[24][25][26]31]. Interestingly, preliminary results using c-fos immunohistochemistry as a marker for neuronal activation suggest that following the delayedphase emetic response, fos is increased most strongly in areas associated with dense SPL-IR fiber plexi (Ray, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…The current mechanistic hypothesis proposes that cisplatin and other emetogens induce a substantial release of serotonin (5-HT) in the gut/enteric nervous system [6,9,19,22,39], and probably the brain as well. Primarily via 5-HT3 receptors (5-HT3R), 5-HT induces a reflex arc mediated through the enteric nervous system and dorsomedial brainstem nuclei including the area postrema (AP), nucleus of the solitary tract (Sol), and dorsal motor nucleus of the vagus nerve (10) [22,26,32]. This hypothesis has been borne out to some degree experimentally, in that 5-HT3R antagonists such as ondansetron and tropisetron are now the first line of antiemetic therapeutics for chemotherapy-related emesis [1,11].…”

Section: Introductionmentioning

confidence: 99%

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A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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Chemotherapy is an effective treatment but difficult to tolerate due to side effects like vomiting. Studies on the etiology of chemotherapy-related emesis have implicated brainstem nuclei and the neurotransmitter Substance P, among other substrates. Since rodents do not vomit, other species have been necessary as alternative models of chemotherapy-induced emesis. Of these, the least shrew (Cryptotis parva) has proven valuable due to its small size, hardiness, and close phylogenetic relationship with primates. However, very little neuroanatomical data on C. parva exist. We used histological and immunohistochemical techniques to provide neuroanatomical data to help validate C. parva as a model organism, especially for emesis research. Brains were sectioned and stained for Nissl substance or myelin, or immunofluorescently labeled for Substance P. Sections were photographed, traced, and reconstructed with standardized zero points, and these data used to create a stereotaxic atlas. The brain of C. parva was similar to but smaller than other mammalian brains, with the cerebellum and hippocampus demonstrating the biggest differences. Differences appeared to be related to the small size of the brain and the metabolic compromises required of such a small mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped, and correlated very well with SPL-IR observed in other species. Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus. These data demonstrate that the anatomical differences between C. parva and other mammals will not preclude its use as a model organism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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“…The NTS receives emetic input from the vagus nerve and AP [7,9]. The NTS neurons receive dual input from the vestibular labyrinth and abdominal vagal nerve, being involved in the control of motion sickness [4,18].…”

Section: Discussionmentioning

confidence: 99%

Emetic Responses and Neural Activity in Young Musk Shrews during the Breast-Feeding/Weaning Period: Comparison between the High and Low Emetic Response Strains Using a Shaking Stimulus

et al. 2005

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“…The conflicting information travels to the vestibular nuclei, through the cerebellum to the vomiting center in the parvicellular reticular formation of the medulla oblongata, and to other brainstem autonomic and hypothalamic areas. The medullary nucleus tractus solitarius represents a site of convergence of different inputs that can elicit nausea and vomiting [Koga and Fukuda, 1992;Bonham and Hasser, 1993;Yates et al, 1994].…”

Section: Pharmaceutical Countermeasures Have Opposite Effects On the mentioning

confidence: 99%

Pharmaceutical Countermeasures Have Opposite Effects on the Utricles and Semicircular Canals in Man

et al. 2012

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Introduction: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. Methods: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. Results: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. Discussion: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA_A-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. Conclusion: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.

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Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs

Cited by 81 publications

References 33 publications

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Emetic Responses and Neural Activity in Young Musk Shrews during the Breast-Feeding/Weaning Period: Comparison between the High and Low Emetic Response Strains Using a Shaking Stimulus

Pharmaceutical Countermeasures Have Opposite Effects on the Utricles and Semicircular Canals in Man

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