Serotonin-independent model of cisplatin-induced emesis in the ferret

para-Chlorophenylalanine (PCPA, 100-200 mg/kg) was used as a pharmacologica l tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the em esis occurring 24 hr after the administration of cisplatin (10 mg/kg) in th e ferret. PCPA was effective to antagonize the initial 8 hr period of retch ing and vomiting, but potentiated the emesis that occurred during the remai ning 8- to 24-hr observation period. Tissue samples removed from the brains tem at 24 hr post injection of cisplatin alone revealed an elevation of 5-H T, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyin doleacetic acid that was similarly antagonized by PCPA. Results are discuss ed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-i nduced emesis in the ferret compared to the problem of acute and delayed em esis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.