Involvement of substance P in the development of cisplatin‐induced acute and delayed pica in rats

Abstract

BACKGROUND AND PURPOSEAlthough substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour. EXPERIMENTAL APPROACHRats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated. KEY RESULTSCisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h. CONCLUSIONS AND IMPLICATIONSThe profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica. Abbreviations

Induction and antagonism of pica induced by teriparatide in rats

“…Kaolin pellets were prepared according to our previous method (Yamamoto et al, 2014). Briefly, pharmaceutical-grade kaolin (hydrated aluminum silicate) was mixed with 3% w/w gum arabic in distilled water to form pellets similar in size to chow pellets and these pellets were then completely dried at room temperature.…”

“…Nausea is defined as a subjective and unpleasant feeling described as recognition of the need to vomit (Quigley et al, 2001); thus, determination of the severity of nausea is rather difficult. We have reported that pica, a behavior characterized by eating non-nutrient materials, such as charcoal, soil, or clay (kaolin), can be used as an assessment of gastrointestinal discomfort and nausea-related response in rats, because this behavior is induced by several emetic stimuli in humans, and it is inhibited by anti-emetic drugs (Yamamoto et al, 2004(Yamamoto et al, , 2007(Yamamoto et al, , 2014. In the present study, in order to develop an animal model for the evaluation of teriparatide-induced nausea, we firstly investigated the effect of teriparatide on the development of pica in rats in different age and gender groups, as well as ovariectomized rats.…”

Administration of Olanzapine as an Antiemetic Agent Changes Glucose Homeostasis in Cisplatin-Treated Rats

“…This is consistent with previous studies from our and other laboratories. 19,30,31) Yamamoto et al 21) showed that 6 mg/kg cisplatin-induced pica was inhibited by both granisetron, a 5-HT 3 receptor antagonist, and aprepitant, a NK 1 receptor antagonist. Furthermore we confirmed that 5 mg/kg cisplatin-induced pica is inhibited by dexamethasone (unpublished data).…”

“…[18][19][20][21][22] However, to our knowledge, the effect of olanzapine on anti-cancer druginduced pica behavior has not been studied.…”

“…16,17) Furthermore, there is increasing evidence that pica can be used for the study of emesis and to screen for the emetic or antiemetic properties of drugs. [18][19][20][21][22] However, to our knowledge, the effect of olanzapine on anti-cancer druginduced pica behavior has not been studied.…”