Action of ondansetron and CP-99,994 to modify behavior and antagonize cisplatin-induced emesis in the ferret

Abstract

The action of ondansetron (1 mg/kg, i.p.) and (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994; 10 mg/kg, i.p.) on spontaneous behavior and the emesis induced by cisplatin (10 mg/kg, i.p.) was studied in the ferret. Ondansetron was inactive to modify behavior, but CP-99,994 reduced spontaneous locomotor activity and lip licking by 48% ( P<0.01) and 79% ( P<0.01), respectively; CP-99,994 also abolished spontaneous burrowing activity ( P<0.05). Treatment of animals with cisplatin induced an emetic response that was abolished by both ondansetron and CP-99,994 ( P<0.01). However, cisplatin did not significantly modify other behavioral measures although animals that received CP-99,994, cisplatin, or CP-99,994 in combination with cisplatin exhibited more episodes of defecation than animals that received ondansetron ( P<0.05). The action of CP-99,994 to modify behavior in this species is discussed in relation to animal models of nausea.