Construction and Application of the Functional Observation Battery for Safety Pharmacology Evaluation in Mice

OBJECTIVE  To establish and apply a functional observation battery(FOB) technique for mice to evaluate the central nervous system(CNS) function of drugs, providing a scientific basis for the safety pharmacology assessments.

METHODS Twenty quarantine-qualified ICR mice(10 males and 10 females) were divided into two experimental groups using stratified randomization based on gender and body weight: the vehicle control group(single intragastric administered 0.9% sodium chloride injection) and the chlorpromazine hydrochloride group(administered 25 mg·kg⁻¹ chlorpromazine hydrochloride solution via single oral gavage). The FOB tests were conducted once for each group of animals before dosing and at 1, 6, and 24 h post-dosing. The tests included cage observations, open-field observations, handling observations, manipulative observations, and special observations. A total of 64 parameters across 4 major dimensions were evaluated: autonomic regulation, motor control and reflexes, emotional and behavioral responses, and central integrative functions. Quantitative scoring was performed to investigate drug effects on mouse CNS function.

RESULTS  Compared with the vehicle control group, significant changes were observed in all 4 dimensions of the observation indicators in the chlorpromazine hydrochloride group from 1 h to 6 h after administration. The animals essentially recovered by 24 h post-dosing.

CONCLUSION  The established FOB technique for mice can serve as an effective tool for the safety pharmacology evaluation of CNS function.