CISPLATIN-INDUCED VOMITING ELIMINATED BY ABLATION OF THE AREA POSTREMA IN CATS

Abstract

Cisplatin[an antineoplastic drug]-induced emesis was characterized using the cat as an experimental model. The incidence, latency and number of vomiting episodes which occurred over an 8-h period were determined for i.v. doses ranging from 3-10 mg/kg. Oscillographic recording of physiologic pressures which produce vomiting served to document the observation that 7.5 mg/kg i.v. was the most effective dose. This dose produced vomiting in 7 animals with a latency of 71 .+-. 7.04 min (mean .+-. SE); subsequent emetic episodes (averaging 3.86/animal) followed a linear relationship with respect to the log of time. The larger dose of 10 mg/kg appeared to be less effective because not all animals responded. Those animals that vomited in response to this dose did so only after a significantly increased latency. Four animals with longstanding lesions of area postrema were tested with cisplatin (7.5 mg/kg); all 4 failed to vomit during a 6-h observation period. In addition, none of the animals exhibited the sustained malaise associated with cisplatin administration to intact animals; only 1 displayed any prodromal emetic signs. The area postrema, the anatomic site of the chemoreceptor trigger zone for emesis, apparently is essential for ciplatin-induced vomiting. Elucidation of this action suggests a possible mechanism for other emetogenic anticancer agents.