CHANGES IN THE AFFERENT ABDOMINAL VAGAL NERVE ACTIVITY-INDUCED BY CISPLATIN AND COPPER-SULFATE IN THE FERRET

In order to clarify the mechanism of drug-induced emesis, the abdomina l afferent vagal nerve activity of anesthetized ferrets was determined . Intravenous bolus injection of 5-hydroxytryptamine (5-HT)(5.0 - 50.0 mu g/kg) produced a dose-dependent increase in abdominal afferent vag al nerve activity. A selective 5-HT3 receptor agonist, 2-methyl-5-HT ( 5.0-50.0 mu g/kg), also increased the abdominal afferent vagal nerve a ctivity in a dose-dependent manner. Increases in vagal nerve discharge s were observed approximately 90 min after the intravenous administrat ion of cisplatin (10mg/kg). Cisplatin-evoked emesis occurred within 90 min after its administration in another batch of ferrets. Afferent va gal nerve activity increased immediately after oral copper sulfate (40 mg/kg) administration. Copper sulfate-induced emesis occurred immedia tely after its administration. Ondansetron, a selective 5-HT3 receptor antagonist, significantly inhibited the increased vagal nerve activit y induced by cisplatin. These findings demonstrated that the activatio n of vagal afferent nerve activity may be relevant to the cisplatin- o r copper sulfate-induced emesis in the ferret. This excitatory respons e of the afferent vagal nerve might be mediated by 5-HT via 5-HT3 rece ptors on the afferent vagal fibers.