MECHANISMS OF CISPLATIN-CHLOROPHENYLBIGUANIDE-INDUCED AND M-CHLOROPHENYLBIGUANIDE-INDUCED EMESIS IN FERRETS

We investigated the involvement of peripheral and central serotonin (5 -HT)3 receptors in cisplatin- and 5-HT3 receptor agonist-induced emesi s in ferrets. Cisplatin (10 mg/kg i.v.)-induced emesis was inhibited b y intravenous YM060 (0.003-0.1 mug/kg). A highly selective and potent 5-HT3 receptor agonist, m-chlorophenylbiguanide (1-10 mg/kg i.p.), dos e dependently elicited emesis an effect which was inhibited by YM060 ( 0.003-0.3 mug/kg i.v.). Vagotomy markedly reduced this emesis, and the combination of abdominal vagotomy and greater splanchnicectomy abolis hed emesis. Lesion of greater splanchnic nerves alone did not markedly inhibit emesis. Intracerebroventricularly (4th ventricle) administere d YM060 inhibited cisplatin- and m-chlorophenylbiguanide-induced emesi s only at higher doses (0.01-0.1 and 0.01-0.03 mug, respectively). Int racerebroventricularly (4th ventricle) administered m-chlorophenylbigu anide (30-100 mug) produced only a weak retching response. These resul ts indicate that stimulation of abdominal vagal afferent nerves via pe ripheral 5-HT3 receptors is important for triggering cisplatin- and m- chlorophenylbiguanide-induced emesis in ferrets.