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 the pica behavior and on the concentration of 5-hydroxyindole acetic acids (5HIAA) in cerebrospinal fluid (CSF) in following adult male five strain rats, Sprague Dawley (SD), Wistar, Fischer344 (F344), Wistar-Imamichi (WI), and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) in rats and kaolin and food intake were measured at 24 hr after the injection of it. Animals were anesthetized with urethane (1 g/kg) at 3 hr after the injection of cyclophosphamide and CSF was collected from cisterna magna. WI and LE rats clearly showed pica behavior as compared to 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-HT3 antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide and pica induced by cyclophosphamide mimics many aspect of emesis including serotonergic response in the central nervous system, and also suggest that using the pica model would be the practical method for the evaluating the effects of anti-emetic drugs in addition to the mechanism of emesis.
