Cisplatin-induced vomiting eliminated by ablation of the area postrema in cats

Cisplatin-induced emesis was characterized using the cat as an experimental model. The incidence, latency, and number of vomiting episodes which occurred over an 8-hour period were determined for iv doses ranging from 3 to 10 mg/kg. Oscillographic recording of physiologic pressures which produce vomiting served to document the observation that 7.5 mg/kg iv was the most effective dose. This dose produced vomiting in seven animals with a latency of 71 +/- 7.04 minutes (mean +/- SE) and subsequent emetic episodes (averaging 3.86/animal) followed a linear relationship with respect to the logarithm 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 four failed to vomit during a 6-hour observation period. In addition, none of the animals exhibited the sustained malaise associated with cisplatin administration to intact animals and only one displayed any prodromal emetic signs. These findings demonstrate that the area postrema, the anatomic site of the chemoreceptor trigger zone for emesis, is essential for cisplatin-induced vomiting. Elucidation of this action suggests a possible mechanism for other emetogenic anticancer agents.