title: Involvement of substance P in the development of cisplatin-induced acute and delayed pica in rats.
abstract: OBJECTIVE
  Although 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.
  
  
  METHODS
  Rats 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.
  
  
  RESULTS
  Cisplatin 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
  The 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.
authors.affiliation: Department of Medical Science and Technology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Asano
authors.forename: Ayana
authors.initials: A
authors.lastname: Tasaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ogura
authors.forename: Seikou
authors.initials: S
authors.lastname: Kim
authors.forename: Yui
authors.initials: Y
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamatodani
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D000970:Antineoplastic Agents; D000077608:Aprepitant; D002945:Cisplatin; D004435:Eating; D017829:Granisetron / Q000494:pharmacology; D007616:Kaolin / Q000008:administration & dosage; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009325:Nausea / Q000139:chemically induced / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D010842:Pica / Q000139:chemically induced / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D000077608:Aprepitant; D002945:Cisplatin; D017829:Granisetron; D007616:Kaolin; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013373:Substance P; D015320:Tachykinins; C044206:preprotachykinin
keywords: 5-HT3 receptor; acute emesis; brain microdialysis; cisplatin; delayed emesis; medulla; neurokinin NK1 receptor; pica; preprotachykinin-A; substance P