Kouichi Yamamoto1, Atsushi Yamatodani2. 1. Department of Medical Science and Technology, Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: kouichi@sahs.med.osaka-u.ac.jp. 2. Osaka University, Japan.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.
INTRODUCTION: 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. METHODS: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. RESULTS: 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). DISCUSSION: 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.