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

Summary.

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 ≈ 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.