Evaluating the effect of donepezil on depression and obsessive–compulsion disorder in mice models and proposing the mechanism involved

Abstract

Introduction: Considering that donepezil (DPZ) is commonly prescribed for Alzheimer’s disease patients, the aim of the present study was evaluating DPZ antidepressant effect and introducing the possible mechanism. Therefore, nicotinic (mecamylamine) and muscarinic (scopolamine) cholinergic antagonists, as well as neurosteroid sigma antagonist (progesterone) effects, were evaluated concomitantly with DPZ. Materials and Methods: The immobility time was measured in male mice, in the forced swimming test (FST) as a model of despair, and the number of marbles buried (MBT) in an open field was assessed as the model of obsessive–compulsive behavior in mice, the tests were verified by fluoxetine. Results and Conclusion: DPZ (1 mg/kg) reduced the immobility time in the FST (117 ± 4.8 s vs. control group 173 ± 3.7 s), the change was similar to fluoxetine (20 mg/kg), which reduced immobility to 52 ± 15 s. The number of marbles buried was reduced by DPZ to 50% in the MBT. Scopolamine (0.5 mg/kg) and mecamylamine (1 mg/kg) that were used concomitantly with DPZ augmented the antidepressant effects of DPZ. While high-dose progesterone (10 mg/kg) not only increased the immobility time (169 ± 7.1 s) but also reversed DPZ effects on the MBT. Conclusion: DPZ agonistic effects on sigma-1 receptor could be responsible for its effects on the immobility time in FST which indicates its antidepression effects. Thus, DPZ should be considered in clinical research for treating depression or obsession in patients with a history of cognition problems, or as an antidepressant in senile dementia.