Improving Effect of Atomoxetine and Reboxetine on Memory in Passive Avoidance Task

Abstract

Objective: The effects of serotonin and/or noradrenaline re-uptake inhibitors on memory have been investigated in various clinical and pre-clinical studies. However, contradictory results have been reported. In this study, the effect of the selective noradrenaline re-uptake inhibitors atomoxetine and reboxetine, a tricyclic antidepressant, amitriptyline, and a selective serotonin re-uptake inhibitor, paroxetine, on learning and memory were examined alone or in combination with scopolamine in mice using a passive avoidance task. Methods: Male Balb-C mice (25-30 g) were used. Reboxetine (10 mg/kg), atomoxetine (5 mg/kg), paroxetine (10 mg/kg) and amitriptyline (10 mg/kg) were investigated alone or in combination with scopolamine (1 mg/kg). A passive avoidance task was used to evaluate memory function. Acquisition time was recorded on the first day and retention time on the second (after 24 h). All drugs and saline were administered intraperitoneally 30 min prior to testing in order to evaluate retention time. Results: None of the drugs or saline impaired retention time when administered alone; however, scopolamine significantly impaired retention time (p=0.003). Reboxetine, atomoxetine and paroxetine all resulted in a marked improvement in retention time in combination with scopolamine. A combination of amitriptyline and scopolamine also significantly reduced retention time (p=0.013). Conclusion: Our results suggest that the effect of atomoxetine and reboxetine on improving memory deficit may be attributed to their inhibition of noradrenaline re-uptake. The effect of paroxetine on improving memory deficit may arise from enhanced serotonergic activity. Amitriptyline's lack of positive effect on memory deficit may be due to its own anticholinergic effect. Further studies using the same models and animal species are needed to clarify the mechanisms of the effects of each drug.