Home cage analysis in double deck rat cages for safety pharmacology: A validation study

Abstract

Home cage analysis (HCA) technologies offer significant 3Rs benefits by measuring individual rodent behavior and physiological parameters within group housed animals. In recent years HCA approaches have been adopted in Safety Pharmacology in single deck cages. Increasingly animal facilities (and rack/cage suppliers) are providing ‘enriched’ double deck cage options for rats. We explored the feasibility of adapting HCA technology to the more complex environment in double deck cage systems and performed a single dose validation study. We adapted a previously published RFID and IR camera-based HCA system to fit a rat double deck cage. Additional RFID detectors covered the mezzanine area. Amphetamine at 0, 1, 3 and 10 mg/kg (n = 6–8 / dose) was tested as an initial reference compound in male Wistar Han rats, dosed AM (3 h into the inactive/light phase) or PM (30 min prior to entering active/dark phase) and effects measured for 24 h after both dosing events. We were able to track each individual animal on the cage base as well as along the mezzanine level including the vertical transitions between the two spatial zones. We could also measure a range of other parameters including activity, body temperature, drinking, rearing, and social proximity. Amphetamine induced dose-dependent increases in general activity, rearing, and body temperature in line with previously reported effects. Specific to the double deck cage, we observed significant increases in transitions between floor levels: a > 6-fold increase (10 mg/kg) after AM dose (next 6 h inactive/light phase), and > 4-fold (10 mg/kg) and > 2-fold (3 mg/kg) increases after PM dose (first 6 h active/dark phase). Results aligned well with data from a parallel IRWIN examination. We show that HCA methods can be adapted to handle more complex environments such as double deck cages for rats. The core parameters obtained reproduce previous published findings for amphetamine. The more complex environment allows us to capture richer behaviors including increased numbers of transitions between the upper and lower decks which all showed dose dependent responses most striking during the PM dosed animals.