Serotonin 5-HT3 receptor antagonists prevent cisplatin-induced emesis in Cryptotis parva: a new experimental model of emesis.

The aim of this manuscript is to introduce Cryptotis parva (the least shrew) as a new experimental emesis model. The chemotherapeutic agent, cisplatin, caused a dose-dependent increase in the number of animals exhibiting vomiting and retching behaviours with ED50 values of 6.43+/-1 and 7.9+/-1.2 mg/kg, respectively. The frequencies of these parameters were also dose-dependent. Intraperitoneal administration of 5-HT3 receptor antagonists (tropisetron or MDL 72222) prevented cisplatin-induced emesis and retching behaviours in the least shrew by a dose-dependent mechanism with respective ID50 values of 4.28+/-2.8 and 2.05+/-2 for emesis, and 2.71+/-4.5 and 2.52+/-2.59 for retching. Intraperitoneal injection of selective and nonselective 5-HT3 receptor agonists potently, and in a dose-dependent fashion, induced emesis in the least shrew with the following ED50 potency order: 2-methyl 5-HT approximately 5-HT (p > 0.05) <5-HTQ (p < 0.01) <mCPBG (p < 0.001). As with other established experimental animal emesis models, the present data indicate that cisplatin causes emesis by activating 5-HT3 receptors indirectly via release of 5-HT.