Induction and antagonism of pica induced by teriparatide in rats

Exploration of Antiemetics for Osteoporosis Therapy-Induced Nausea and Vomiting Using PET Molecular Imaging Analysis to Gastrointestinal Pharmacokinetics

“…Although these mechanisms require further clarification, the results presented here indicate that the teriparatide-induced decrease in intestinal absorption of [ 18 F]FDG may be due primarily to serotonergic reactions, not cholinergic. In fact, Yamamoto et al clearly demonstrated that treatment with granisetron and prochlorperazine completely inhibited teriparatide-induced pica, a behavior characterizing by eating non-nutrient materials, and suggested that serotonin 5-HT 3 receptor and histamine H 1 antagonists potentially possess therapeutic effects on teriparatide-induced nausea (20). This observation supports our findings.…”

“…Mosapride is a selective 5-HT 4 receptor agonist that facilitates the release of locally endogenous acetylcholine and is thought to selectively stimulate upper, but not lower, GI motility, and to have no effects on the central nervous system (CNS) (27)(28)(29). The mechanism of action of prochlorperazine has not been fully determined, but has been attributed to dopamine and histamine blockade in the chemoreceptor trigger zone (19,20,30). The pharmacologic properties of mosapride and prochlorperazine indicate that inhibiting the pharmacological activity of teriparatide either peripherally or centrally is insufficient to reverse the teriparatide-induced decrease in the GI absorption of [ 18 F]FDG.…”

Detection of Nausea-Like Response in Rats by Monitoring Facial Expression

“…From these findings, since the results of this study are not considered to be due to the early development of neuropathy, which would probably require more time to occur, they may indicate a method for the detection of the nausea-like response in rats. We previously reported that copper sulfate, lithium chloride, and teriparatide (parathyroid hormone analog) transiently increased only kaolin consumption without affecting food consumption in rats (Yamamoto et al, 2004, 2015). Takeda et al (1986) reported that rotation stimulation induced pica behavior in rats.…”

“…Previous studies reported that salivation, conditioned taste aversion, gaping, secretion of vasopressin, and gastric stasis are closely associated with the development of nausea (Andrews and Horn, 2006; Cabezos et al, 2008; Parker, 2014; Scallan and Simon, 2016), but it is difficult to accurately measure these parameters in laboratory animals under physiological conditions. We previously suggested that pica behavior in rats can be used as a method to assess gastrointestinal malaise including nausea (Yamamoto et al, 2014, 2015, 2016). The amount of kaolin intake in rats is proportional to the emetogenicity in humans (Yamamoto et al, 2007).…”

“…Rats, one of the most common laboratory animals, have been considered unsuitable for the study of nausea and vomiting because they do not show a vomiting reflex (Hatcher, 1924). We previously reported that pica behavior, a behavior seen in rats characterized by eating non-nutritive materials, such as clay (kaolin), has been considered as a model of a nausea-like response or gastrointestinal malaise because it is induced by nauseant stimuli and the amount of kaolin intake is related to the nauseant severity in humans (Yamamoto et al, 2007, 2011, 2014, 2015, 2016). However, previous studies reported that it is difficult to evaluate their nausea-like response by the amount of kaolin intake, because rats subjected to marked stimuli showed decreased feeding and locomotive behaviors due to behavioral suppression (Malik et al, 2006, 2007; Cabezos et al, 2008).…”