Use of the Actiwatch-Mini® in dog safety studies as an early indicator for drug-induced behavioural changes

Abstract

IntroductionClinical observations are routinely used to address drug-induced behavioural changes in dogs. To deal with the limitations of this methodology, we evaluated Actiwatch-Mini® as a tool to monitor continuously locomotor activity in dogs and to provide objective parameters that could be linked to behavioural changes after compound administration. MethodsEight Beagles were equipped with Actiwatch-Mini®. As a reference drug, a PDE2-inhibitor was administered daily for six days at doses known to cause minor or severe behavioural changes. ResultsWhile traditional observation showed no behavioural changes - except sedation - dogs receiving 0.5 mg/kg/day, showed significant increases in % immobile time (+15.8%) and mean length of immobile phases (+1.2 min) but no change in number of immobile phases (+2.2). At 1 mg/kg/day, light to severe changes in behaviour were present. Actiwatch-Mini® recorded an increase in mean length of immobile phases (+1.9 min) and a decrease in mean number of immobile phases (−7.4) in the first four hours after each dosing while total % immobile time was not significantly increased (+4.9%). DiscussionActiwatch-Mini® was able to detect changes in immobility parameters in dogs dosed with a PDE2-inhibitor while no or only minor behavioural changes were observed. The system can be used for continuously monitoring the activity of dogs, to provide objective scores for evaluation of activity. It provides an inexpensive and low labour-intensive method for detecting changes in activity and possible early indications of drug-induced behavioural changes.