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

Azadeh Mesripour, Valiollah Hajhashemi, Shahrzad Rezaie

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. Material 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 (117sec ± 4.8; vs control group 173sec ± 3.7), and reduced the number of marbles buried by 50 % in the MBT. Neither scopolamine (0.5 mg/kg), nor mecamylamine (1 mg/kg) that were used concomitantly with DPZ reversed the antidepressant effects of DPZ. While high dose progesterone (10 mg/kg), not only increased the immobility time (169sec ± 7.1) but also reversed DPZ effects on the MBT. Therefore DPZ has beneficial effects on affective disorders. Thus DPZ could be promising in treating depression or obsession in patients with history of cognition problems, or as an antidepressant in senile dementia. DPZ agonistic effects on sigma-1 receptor could be responsible for its beneficial effects on depression.

 


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