Reserpine, para-chlorophenylalanine and fenfluramine antagonise cisplatin-induced emesis in the ferret

Abstract

The involvement of 5-hydroxytryptamine (5-HT) with cisplatin-induced emesis in the ferret was investigated using reserpine, para-chlorophenylalanine and fenfluramine. Pretreatment with reserpine (5 mg/kg, 24 hr), fenfluramine (5 mg/kg, 4 days) or para-chlorophenylalanine (100 or 400 mg/kg, 4 days) antagonised cisplatin-induced emesis. All treatments reduced the levels of 5-HT in the area postrema and at other cerebral sites, but whilst this action was relatively selective for small doses of para-chlorophenylalanine [only modest effects on noradrenaline (NA) and no change in the content of dopamine (DA) in the area postrema], other treatments reduced levels of dopamine and noradrenaline. Data are discussed in terms of an involvement of 5-HT/catecholamines in the area postrema with the mediation of emesis induced by cisplatin.