Applying Digital Measures to Assess Dose-Dependent Effects of a Neuroactive Compound in Mice

Traditional behavioral assessments in preclinical research often rely on manual observations that can be subjective and prone to variability. Digital home-cage monitoring systems offer an objective, continuous, and non-invasive method for quantifying behavioral changes in animal models. This study aimed to evaluate the ability of digital behavioral phenotyping to detect dose-dependent effects of neuroactive compounds.EnvisionTM by the Jackson Laboratory is an advanced digital in vivo monitoring system designed to assess mouse behavior and physiology in the home cage environment and was used to monitor mice continuously throughout the study. The study design configured in Envision included continuous digital measurement of Activity Suite (Activity, Activity Classification, and Distance Travelled in the Locomotor Activity Bouts) as well as Respiratory Rate for individual mice. Female 11-week-old C57BL/6J female mice (n=18) were housed in Allentown Discovery™ IVC cages and were acclimated to the cages for 7 days. Mice were treated with 5 or 25 mg/kg morphine or vehicle, which was administered at the beginning of both the light and dark cycle and were monitored for 48 hours.Using the Envision Activity Suite, dose-dependent behavioral and physiological effects of morphine were clearly identified. The system effectively classified animal behavior into activity categories, revealing a statistically significant increase in locomotion with morphine. At 25 mg/kg, mice exhibited locomotor behavior for a median of 78.6% of the three-hour post-dose period, compared to 17.1% for the 5 mg/kg dose and 2.8% for the vehicle group. Respiratory rate analysis showed a similar dose-dependent pattern, with significant changes in the 3 hours following treatment for both doses, with sustained effects (3-6 hours) in mice treated with 25 mg/kg. All groups returned to baseline by 6-9 hours.This study demonstrates that computer vision based digital measures from the home cage were effective at detecting dose-dependent effects of morphine on the activity and respiration in mice, representing a powerful advancement in preclinical research and offering rich, high-resolution insights that can improve decision-making in drug development and accelerate the translation of findings into clinical success.