Development of a mouse model to determine the systemic activity of potential flea-control compounds

Probe studies were performed to determine if the cat flea ( Ctenocephalides felis), the most common ectoparasite of companion animals, will feed on laboratory mice and, if so, to incorporate this into a small animal assay to detect systemically active compounds. Consequently, a protocol was developed which incorporated acepromazine maleate to temporarily sedate various strains of mice and allow fleas a window of time to feed undisturbed. For validation of the model, CD-1 mice were dosed per os with seven known insecticides at 30, 10 and 1 mg/kg. Mice were sedated with 0.0125 ml acepromazine maleate intraperitoneally, and infested with fleas. After 2 h, fleas were removed, one-third were examined immediately to confirm the occurrence of feeding, and 77% were found to have ingested a blood meal. The remaining fleas were incubated for 24 h to determine mortality. Nitenpyram, the active ingredient in Capstar™, was highly active (>94%) at 1 mg/kg. Selamectin, the active ingredient in Revolution™, was very active (86%) at 10 mg/kg, but inactive at 1 mg/kg. Fipronil, the active ingredient of Frontline ® Topspot™, was very active (83%) at 30 mg/kg, moderately active (54%) at 10 mg/kg and inactive at 1 mg/kg. Cythioate, the active ingredient in Proban ®, and nodulisporic acid, a recently discovered oral insecticide, were moderately active (64 and 55%, respectively) at 10 mg/kg, but both were inactive at 1 mg/kg. Lufenuron and ivermectin exhibited no efficacy at any level tested. These findings suggest that this mouse model can effectively identify systemic flea-control leads and, subsequently, reduce the use of large animals in research.