Subchronic Amitriptyline Influences Open-field Behaviours and Spontaneous Working-memory in Healthy Mice

Abstract

Objective: We assessed the effects of amitriptyline on open-field locomotion, stereotypic behaviours and spatial working-memory in healthy mice. Method: Five groups of mice were administered vehicle (distilled water), scopolamine (2 mg/kg), or one of three doses of amitriptyline (5, 10 and 15 mg/kg) for 21 days. Behaviours were assessed after the first and final dose of treatment. Result: Administration of the first dose of amitriptyline was associated with enhanced open-field horizontal locomotion, rearing and grooming; with repeated administration, there was suppression of horizontal locomotion and rearing. A dose-related decrease in Y-maze and radial-arm maze spatial working-memory was also observed after repeated administration. Compared to scopolamine, amitriptyline was associated with a significant reduction in open-field behaviours, but a significantly-higher spatial working-memory score. Conclusion: Repeated administration of amitriptyline in healthy mice was associated with suppression of locomotion and grooming; working-memory deficits were also observed. However, working-memory task performance is significantly better than the scopolamine group.