title: Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.
abstract: It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.
authors.affiliation: Laboratory Animal Research Center, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan. tohei@dokkyomed.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tohei
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hokao
authors.forename: Motoo
authors.initials: M
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D007616:Kaolin / Q000008:administration & dosage*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010842:Pica / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012702:Serotonin Antagonists; D007616:Kaolin; D017294:Ondansetron; D006897:Hydroxyindoleacetic Acid; D003520:Cyclophosphamide