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.