Behavioral studies of emetic sensitivity in the ferret

Knox, A.P.; Strominger, Norman L.; Battles, August H.; Carpenter, David O.

doi:10.1016/0361-9230(93)90112-o

Cited by 46 publications

(32 citation statements)

References 63 publications

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“…In general, rats lack the vomiting center in the brain and therefore cannot vomit (King et al, 1999). Nevertheless, the rat model responds consistently to a variety of feeding behaviors inducing stimuli, such as CP and ionizing radiation (King, 1990;Knox et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats

Sathyanath

Rao

Kim

et al. 2013

Pharmaceutical Biology

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Context: Nausea and vomiting are considered as the foremost unpleasant side effects of chemotherapy experienced by 20-90% of cancer patients. Objective: In the present study, the effects of Korean Panax ginseng C.A. Meyer (Araliaceae) (RG), ginseng saponin (GS) and non-saponin (GNS) on cisplatin (CP)-induced pica and gastric damage in rats were investigated. Material and methods: Rats were treated with RG (25, 50, 100 mg/kg b.wt.), GS (5 and 10 mg/kg 100 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) before or after a single intraperitoneal injection of CP (6 mg/kg b.wt.). Kaolin together with normal food intake, normal food alone, body weight, histological examination of stomach and small intestine were used as indices of CP-induced pica in rats. Results: Pre-treatment with RG (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake at 24 h. CP-induced kaolin intake decreased upon post-treatment of rats with RG (50 and 100 mg/ kg b.wt.) at 48 h. The incidence of body weight reduction at 48 and 72 h diminished in rats posttreated with RG (50 mg/kg b.wt.). Pre-treatment with GS (5 and 10 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake while normal food intake was not improved in 24 and 48 h. Discussion and conclusion: The gastro-protective effects of RG, GS and GNS were further confirmed by histopathological (damage in glandular portion and villi with dilated appearance) findings. The study indicates that both the red GS and GNS improve feeding behavior against CP-induced pica in rats.

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Section: Discussionmentioning

confidence: 99%

Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats

Sathyanath

Rao

Kim

et al. 2013

Pharmaceutical Biology

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“…[8,63]. However, in ferrets the opposite effect was noted [21,32]. Intravenous administration of the NK 1 receptor antagonist RPR100893 was effective against cisplatin-induced emesis in ferrets, but did not reduce foot-tapping in gerbils [49].…”

Section: Introductionmentioning

confidence: 99%

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

et al. 2008

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Substance P (SP) is thought to play a cardinal role in emesis via the activation of central tachykinin NK 1 receptors during the delayed phase of vomiting produced by chemotherapeutics. Although the existing supportive evidence is significant, due to lack of an appropriate animal model, the evidence is indirect. As yet, no study has confirmed that emesis produced by SP or a selective NK 1 receptor agonist is sensitive to brain penetrating antagonists of either NK 1 , NK 2 , or NK 3 receptors. The goals of this investigation were to demonstrate: 1) whether intraperitoneal (i.p.) administration of either SP, a brain penetrating (GR73632) or non-penetrating (e.g. SarMet -SP) NK 1 receptor agonist, an NK 2 receptor agonist (GR64349), or an NK 3 receptor agonist (Pro 7 -NKB), would induce vomiting and/or scratching in the least shrew (Cryptotis parva) in a dose-dependent manner; and whether these effects are sensitive to the above selective receptor antagonists; 2) whether an exogenous emetic dose of SP (50 mg/kg, i.p.) can penetrate into the shrew brain stem and frontal cortex; 3) whether GR73632 (2.5 mg/kg, i.p.)-induced activation of NK 1 receptors increases Fos-measured neuronal activity in the neurons of both brain stem emetic nuclei and the enteric nervous system of the gut; and 4) whether selective ablation of peripheral NK 1 receptors can affect emesis produced by GR73632. The results clearly demonstrated that while SP produced vomiting only, GR73632 caused both emesis and scratching behavior dose-dependently in shrews, and these effects were sensitive to NK 1 -, but not NK 2 -or NK 3 -receptor antagonists. Neither the selective, non-penetrating NK 1 receptor agonists, nor the selective NK 2 -or NK 3 -receptor agonists, caused a significant dose-dependent behavioral effect. An emetic dose of SP selectively and rapidly penetrated the brain stem but not the frontal cortex. Systemic GR73632 increased Fos expression in the enteric nerve plexi, the medial subnucleus of nucleus tractus solitarius, and the dorsal motor nucleus of the vagus, but not the area postrema. Ablation of peripheral NK 1 receptors attenuated the ability of GR73632 to induce a maximal frequency of emesis and shifted its percent animals vomiting dose-response curve to the right. The NK 1 -ablated shrews exhibited scratching behavior after systemic GR73632-injection. These results, for the first time, affirm a cardinal role for central NK 1 receptors in SP-induced vomiting, and a Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. facilitatory role for gastrointestinal NK 1 receptors. In addition, the...

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“…Substance P-containing fibers and tackykinin NK 1 receptors are present in the solitary nucleus, a part of the emetic center (4,5). Administration of substance P produced emesis in ferrets (6). Injection of an NK 1 -receptor antagonist into the vicinity of the solitary nucleus inhibited cisplatin-induced emesis (7).…”

Section: Introductionmentioning

confidence: 99%

Long-Lasting Anti-emetic Effect of T-2328, a Novel NK1 Antagonist

Watanabe¹,

Okamoto

Ishii³

et al. 2008

J Pharmacol Sci

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Abstract. The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl] amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK 1 -receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, respectively. Ondansetron, a 5-HT 3 antagonist, almost completely blocked the acute emesis and transiently reduced the delayed emesis. In contrast, T-2328 elicited long-lasting anti-emetic effects on both acute and delayed phases by a single intravenous administration. Suppression of delayed emesis was not due to elimination of the acute phase because the delayed emesis was also suppressed by administration after the onset of delayed emesis. Persistent blockade of NK 1 receptors in the brain was demonstrated by inhibition of the NK 1 agonist-induced foot tapping response for over 24 h. An appreciable amount of T-2328 was present in the brain 32 and 72 h after the injection. The NK 1 agonistinduced contractions of isolated ileum in guinea pigs was antagonized with IC 50 values of 1.4 nM in an insurmountable manner. It is likely that T-2328 exerts the long-lasting anti-emetic effect by not only long-term presence in the brain but also its insurmountable inhibition of NK 1 receptors.

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Behavioral studies of emetic sensitivity in the ferret

Cited by 46 publications

References 63 publications

Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats

Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

Long-Lasting Anti-emetic Effect of T-2328, a Novel NK1 Antagonist

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