title: Induction and antagonism of pica induced by teriparatide in rats.
abstract: Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.
authors.affiliation: Department of Medical Science and Technology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan. Electronic address: kouichi@sahs.med.osaka-u.ac.jp.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Medical Affairs Department, Pharmaceutical Business Administration Division, Asahi Kasei Pharma Corporation, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kato
authors.affiliation: Medical Affairs Department, Pharmaceutical Business Administration Division, Asahi Kasei Pharma Corporation, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Isogai
authors.affiliation: Medical Affairs Department, Pharmaceutical Business Administration Division, Asahi Kasei Pharma Corporation, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Medical Science and Technology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Professor Emeritus, Osaka University, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamatodani
mesh_terms: D000367:Age Factors; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D000932:Antiemetics / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology; D004195:Disease Models, Animal; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D017829:Granisetron / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007616:Kaolin; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009325:Nausea / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010052:Ovariectomy; D010842:Pica / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D011346:Prochlorperazine / Q000494:pharmacology; D017208:Rats, Wistar; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D019379:Teriparatide
chemical_list: D000932:Antiemetics; D004155:Diphenhydramine; D065127:Dopamine D2 Receptor Antagonists; D017829:Granisetron; D006634:Histamine H1 Antagonists; D007616:Kaolin; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D011346:Prochlorperazine; D058831:Serotonin 5-HT3 Receptor Antagonists; D019379:Teriparatide; C579707:fosaprepitant
keywords: Anti-emetic drugs; Nausea; Ovariectomized rats; Pica; Teriparatide