Serotonin-Independent Model of Cisplatin-Induced Emesis in the Ferret

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  • Rudd John A.
    Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong
  • Cheng Celine H.K.
    Postgraduate Studies in Pharmacology, The School of Pharmacy, University of Bradford
  • Naylor Robert J.
    Postgraduate Studies in Pharmacology, The School of Pharmacy, University of Bradford

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  • Serotonin-Independent Model of Cisplati

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Abstract

para-Chlorophenylalanine (PCPA, 100 - 200 mg/kg) was used as a pharmacological tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the emesis occurring 24 hr after the administration of cisplatin (10 mg/kg) in the ferret. PCPA was effective to antagonize the initial 8 hr period of retching and vomiting, but potentiated the emesis that occurred during the remaining 8- to 24-hr observation period. Tissue samples removed from the brainstem at 24 hr post injection of cisplatin alone revealed an elevation of 5-HT, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyindoleacetic acid that was similarly antagonized by PCPA. Results are discussed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-induced emesis in the ferret compared to the problem of acute and delayed emesis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.

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