Species-level differences between mice and rats in regards to micronucleus induction with the hypothermia-inducing drug haloperidol

Abstract

Species-level differences in response to micronucleus induction with haloperidol, a drug that can induce hypothermia, were investigated. Haloperidol was intraperitoneally (i.p.) administered to mice (12.5–50 mg/kg) and rats (25–100 mg/kg), and the rectal temperature was then measured. At every investigated dose, haloperidol transiently decreased the rectal temperature in mice to less than 30 °C. However, the rectal temperature decreased to approximately 34 °C in rats. For micronucleus induction, haloperidol at doses of 25 and 50 mg/kg resulted in a statistically significant increase in micronucleated polychromatic erythrocyte frequency in the 48 h sampling group of mice, but not in rats. In addition, relatively large micronuclei (diameter of micronucleus > one-fourth the diameter of the cytoplasm) accounted for 46–47% of the induced micronuclei in mice, suggesting that hypothermia affected the mitotic apparatus. Thus, hypothermia can induce micronuclei in vivo as a secondary effect, and the hypothermic response to haloperidol in mice was stronger than that of rats. Micronuclei could only be induced in mice during this study. Therefore, species-level differences may exist in regards to micronucleus induction by hypothermia-inducing drugs.