Strain differences in the development of cisplatin-induced pica behavior in mice

Pica behavior, kaolin ingestion, in rats and mice can be used as an assessment of nausea and vomiting; however, we observed that the incidence of pica behavior in ICR strain mice varied markedly. We investigated the susceptibility of four strains of mice (ICR, BALB/c, C57BL/6, and DBA/2) to the development of pica behavior.

Mice received cisplatin (7.5 mg/kg, i.p.) with or without a serotonin 5-HT₃ receptor antagonist (granisetron: 0.1 mg/kg, i.p.) or tachykinin NK₁ receptor antagonist (fosaprepitant: 30 mg/kg, i.p.), and then their daily kaolin intake was measured for 2 days. We examined the expression of preprotachykinin (PPT)-A mRNA in the medulla of cisplatin-treated mice 8 and 32 h after drug administration.

All mice except for ICR strain significantly increased kaolin intake after cisplatin administration. Among the tested strains, DBA/2 mice compared to BALB/c and C57BL/6 mice notably showed pica behavior on both days (P < 0.0001). The expression of PPT-A mRNA was significantly increased 8 h after cisplatin administration in all strains, but the increase remained on the second day only in DBA/2 mice (P < 0.05). Granisetron significantly inhibited pica behavior in DBA/2 mice on the first day (P < 0.0001), but not the second day; however, fosaprepitant completely inhibited the pica behavior on both days (P < 0.001).

These results indicate that cisplatin-induced pica behavior in mice is likely to be influenced by the genotype, and that DBA/2 mice are useful to analyze the emetogenic or anti-emetic potential of drugs in preclinical studies.